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Delivered record second quarter Total income, Total Cash Receipts and Adjusted EBITDA Delivered Adjusted EBITDA margin of 92% Subsequent to the end of the quarter, DRI Healthcare exercised its contractual put option on Ekterly for a total net repurchase price of ~$178M TORONTO , Aug. 7, 2026 /CNW/ -- DRI Healthcare Trust (TSX: DHT.UN) (TSX: DHT.U) ("DRI Healthcare") today announced its financial results for the quarter ended June 30, 2026. DRI Healthcare's second quarter 2026 financial statements and Management's Discussion & Analysis ("MD&A") have been filed on SEDAR+ ( ). All dollar amounts are expressed in U.S. dollars unless otherwise indicated. "We are pleased to have delivered another solid quarter, posting record financial performance with double-digit growth across Total income, Cash Receipts and Adjusted EBITDA" said Ali Hedayat, Chief Executive Officer. "We also achieved two important milestones in our pre-approval portfolio. In June, Viridian's veligrotug, now named Lumvoa, received FDA approval. Following quarter-end, we exercised our put option on Ekterly for a total net repurchase price of approximately $178 million, which represents a return of 1.5x our purchase price and a high 20s IRR. Together, the Ekterly and Lumvoa outcomes demonstrate our underwriting team's discipline and specialized expertise across the full cycle of an asset - from regulatory approval to realized returns for Unitholders." Q2 Highlights Total income of $50.1 million; Total Cash Receipts of $46.5 million 1 ; Adjusted EBITDA of $42.6 million 1 ; Comprehensive earnings of $7.5 million; Adjusted Cash Earnings per Unit of $0.56 (basic and diluted) 1, 2 ; Repurchased 89,513 Units under its current and previous Normal Course Issuer Bid plans ("NCIB Plans") at an average price of $11.65, totaling $1.0 million; and Paid a quarterly cash distribution of $0.11 per Unit on July 20, 2026 to Unitholders of record on June 30, 2026. Subsequent to Quarter End ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); DRI Healthcare exercised its contractual put option (the "Put Option") with respect to its royalty participation right in Ekterly, for a total net repurchase price of approximately $178 million; On July 10, 2026, DRI Healthcare made a milestone payment of $75 million to Viridian, following the U.S. Food and Drug Administration ("FDA") approval of Lumvoa (veligrotug) for the treatment of thyroid eye disease ("TED"); and Declared a quarterly distribution of $0.11 per Unit in the third quarter of 2026, payable on October 20, 2026 to Unitholders of record on September 30, 2026. _______________________________________ 1 Total Cash Receipts and Adjusted EBITDA are non-GAAP financial measures. Adjusted Cash Earnings (Loss) per Unit is a non-GAAP ratio. These measures are not standardized measures under IFRS and might not be comparable to similar financial measures disclosed by other issuers. The reconciliation of these measures can be found later in this news release and in DRI Healthcare's second quarter 2026 MD&A. 2 The weighted average number of basic and diluted Units for the purposes of calculating Earnings (Loss) per Unit for the three months ended June 30, 2026 were 55,007,167 Units and 55,374,923 Units, respectively. Appointment of Dr. Sheila Singh and Dr. Yasir Al-Wakeel to Board of Trustees DRI Healthcare is pleased to announce that its board of trustees has increased its size by one and appointed Dr. Sheila Singh and Dr. Yasir Al-Wakeel, effective immediately. "We are delighted to welcome Sheila and Yasir to our board. Together, they bring broad experience spanning the biopharmaceutical and finance industry. Their leadership and passion for innovation will be invaluable as we continue to execute our strategy and build DRI Healthcare for the long term" said Ali Hedayat. Dr. Singh is an internationally recognized neurosurgeon-scientist whose career spans patient care, scientific discovery, translational research, institutional leadership, and biotechnology commercialization. She is the Richard Dimbleby Professor of Cancer Research, Joint Head of the School of Cancer & Pharmaceutical Sciences and Head of the Comprehensive Cancer Centre at King's College London, Professor of Neuro-oncology and Neurosurgery, and a senior strategic advisor to Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust. Dr. Singh is also Professor of Surgery and Biochemistry (part time) at McMaster University, where she was also the founding Director of the Centre for Discovery in Cancer Research (CDCR). Dr. Al-Wakeel is a seasoned biotechnology executive and board member with a track record of building and leading life sciences companies from early stage through commercialization. He currently serves as Chief Executive Officer of Vesalius Therapeutics and as a CEO-Partner at Flagship Pioneering. Earlier in his career, he held senior positions as a biotech equity analyst and in corporate finance, where he led or advised on more than US$30 billion in strategic and financial transactions. A physician-scientist by training, he also held clinical and academic medical posts in the United Kingdom. This combination of clinical, financial, and operational experience positions him to guide biotechnology companies through the full arc of scaling a business and bringing medicines to patients. DRI Healthcare also announced that Kevin Layden will be resigning from the board of trustees in order to focus on his full-time responsibilities. Mr. Hedayat also noted, "We would like to thank Kevin for his significant contributions to the board since joining in 2021. His perspective and insights have been particularly valuable in assisting DRI Healthcare." Financial Highlights Three months ended Six months ended (thousands of U.S. dollars, except per Unit amounts) June 30, 2026 June 30, 2025 June 30, 2026 June 30, 2025 Total income 50,077 44,130 98,721 88,158 Amortization of intangible royalty assets 25,464 24,751 50,412 49,496 Management fees -- 2,657 -- 6,733 Performance fees -- -- -- 533 Other expenses 15,398 15,375 32,604 31,801 Gain (loss) on debt refinancing -- (971) (9,794) (971) Net unrealized gain (loss) on derivative instruments (1,765) -- (1,512) -- Net unrealized gain (loss) on foreign exchange remeasurement 1,603 -- 3,267 -- Net earnings (loss) before tax 9,053 376 7,666 (1,376) Income tax recovery (expense) (3,031) -- (2,628) -- Net earnings (loss) 6,022 376 5,038 (1,376) Net unrealized gain (loss) on derivative instruments 1,514 (1,076) 2,957 (1,156) Comprehensive earnings (loss) 7,536 (700) 7,995 (2,532) Net earnings (loss) per Unit – basic 0.11 0.01 0.09 (0.02) Net earnings (loss) per Unit – diluted 0.11 0.01 0.09 (0.02) Total Cash Receipts 1 46,455 40,152 104,811 102,142 Adjusted EBITDA 1 42,564 30,372 95,315 82,031 Adjusted EBITDA Margin 1 92 % 76 % 91 % 80 % Adjusted Cash Earnings per Unit – basic 1 0.56 0.51 1.24 0.95 Adjusted Cash Earnings per Unit – diluted 1 0.56 0.51 1.24 0.95 Weighted average number of Units – basic 55,007,167 55,685,363 55,023,166 55,743,876 Weighted average number of Units – diluted 55,374,923 55,685,363 55,244,232 55,743,876 Asset Performance As at June 30, 2026, DRI Healthcare's portfolio included 28 royalty streams on 22 products that address a variety of therapeutic areas, such as oncology, neurology, ophthalmology, endocrinology, hematology, dermatology, lysosomal storage disorders ("LSD") and immunology. On June 30, 2026, the intangible royalty asset portfolio had a book value, net of accumulated amortization and impairments, of $808.9 million, which during the three and six months ended June 30, 2026 generated Total Cash Royalty Receipts 1 of $46.5 million and $104.8 million, respectively, and royalty income of $48.2 million and $94.8 million, respectively. On June 30, 2026, the financial royalty assets had a book value of $55.6 million, which during the three and six months ended June 30, 2026 generated a change in its fair value of $1.7 million and $3.3 million, respectively. _______________________________________ 1 Total Cash Receipts and Adjusted EBITDA are non-GAAP financial measures. Adjusted EBITDA Margin and Adjusted Cash Earnings (Loss) per Unit are non-GAAP ratios. These measures and ratios are not standardized measures under IFRS and might not be comparable to similar financial measures disclosed by other issuers. The reconciliation of these measures can be found later in this news release and in DRI Healthcare's second quarter 2026 MD&A. Portfolio (thousands of U.S. dollars) Cash Receipts Three months ended Six months ended Royalty Asset Therapeutic Area Primary Marketer(s) June 30, 2026 June 30, 2025 June 30, 2026 June 30, 2025 Casgevy Hematology Vertex Pharmaceuticals -- -- 5,000 5,000 Ekterly Immunology KalVista 2,163 -- 3,992 -- Empaveli/Syfovre Hematology/Ophthalmology Apellis, Sobi 149 147 1,311 1,272 Eylea I Ophthalmology Regeneron, Bayer, Santen 1,022 1,158 2,139 2,680 Eylea II Ophthalmology Regeneron, Bayer, Santen 215 248 453 579 Omidria Ophthalmology Rayner Surgical 8,347 8,993 17,031 16,987 Oracea Dermatology Galderma 890 1,046 1,851 2,580 Orserdu I Oncology Menarini 8,279 6,410 19,879 14,287 Orserdu I – milestone Oncology Menarini -- -- 5,000 633 Orserdu II Oncology Menarini 8,279 6,409 18,581 23,806 Orserdu II – milestone Oncology Menarini -- -- -- 5,523 Rydapt Oncology Novartis 563 777 1,356 1,936 Spinraza Neurology Biogen 3,717 3,781 7,351 7,743 Vonjo I Hematology Sobi 2,879 2,553 5,988 5,648 Vonjo II Hematology Sobi 608 576 1,302 1,351 Xenpozyme Lysosomal Storage Disorder Sanofi 2,879 1,913 2,879 1,913 Xenpozyme - milestone Lysosomal Storage Disorder Sanofi 450 -- 450 -- Xolair Immunology Roche, Novartis 2,698 2,162 5,197 4,535 Zejula Oncology GSK 993 1,103 2,010 2,052 Zytiga Oncology Johnson & Johnson 1,762 2,230 1,762 2,230 Other Products 1 Various Various 562 646 1,279 1,387 Total Cash Receipts, Normalized Cash Receipts and Cash Royalty Receipts 2 46,455 40,152 104,811 102,142 Liquidity and Capital As at June 30, 2026, DRI Healthcare had cash and cash equivalents of $55.2 million. As at June 30, 2026, DRI Healthcare's long-term debt of $372.3 million was composed of i) $29.1 million on the long-term portion of its credit facility; (ii) $31.0 million of preferred securities; (iii) $64.8 million convertible debentures; and iv) $247.4 million on its senior notes. As at June 30, 2026, DRI Healthcare had 54,963,322 Units issued and outstanding. Distributions On May 14, 2026, the board of trustees of DRI Healthcare declared a quarterly cash distribution of $0.11 per Unit for the second quarter of 2026, which was paid on July 20, 2026 to Unitholders of record as of June 30, 2026. Today, the board of trustees of DRI Healthcare declared a quarterly cash distribution of $0.11 per Unit for the third quarter of 2026, payable on October 20, 2026, to Unitholders of record as of September 30, 2026. ______________________________________ 1 Other Products includes royalty income from certain other intangible royalty assets as well as intangible royalty assets which are fully amortized and, where applicable, the entitlements to which have generally expired. Comparative figures for royalty assets Natpara are included in Other Products. 2 Total Cash Receipts, Normalized Cash Receipts and Cash Royalty Receipts are non-GAAP financial measures. These measures are not standardized measures under IFRS and might not be comparable to similar financial measures disclosed by other issuers. The reconciliation of these measures can be found later in this news release and in DRI Healthcare's second quarter 2026 MD&A. Ekterly Disposition Subsequent to June 30, 2026, DRI Healthcare exercised its Put Option with respect to its royalty participation right in Ekterly, for a total net repurchase price of approximately $178 million. The Put Option has been exercised following the acquisition of KalVista by Chiesi Group on June 11, 2026. Subject to the terms of the royalty agreement, DRI Healthcare expects to receive payment no later than mid-August 2026. The Ekterly royalty purchase agreement will terminate upon receipt of the put price. Lumvoa (veligrotug) and Elegrobart Royalty Transaction On June 26, 2026, the U.S. FDA approved Lumvoa (veligrotug) for the treatment of TED. In connection with this approval, DRI Healthcare recognized a milestone payable of $75 million to Viridian during the three months ended June 30, 2026, which reduced DRI Healthcare's maximum remaining potential milestone obligation to $130 million. On July 10, 2026, DRI Healthcare made a milestone payment of $75 million to Viridian pursuant the term of its existing royalty agreement. On July 9, 2026, DRI Healthcare drew $50 million from its acquisition credit facility to partially fund the payment. Second Quarter 2026 Conference Call & Webcast As previously announced, management will hold a conference call on Monday, August 10, 2026 at 8:00 a.m. (ET) to review DRI Healthcare's second quarter 2026 results. Interested parties can join the call by dialing 1-888-699-1199 or 416-945-7677 approximately 15 minutes prior to the call to secure a line. A live webcast of the conference call, including a slide presentation, will be available at . Please connect at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to join the webcast. The webcast will be archived on DRI Healthcare's website at drihealthcare.com/investors following the conference call date. Non-GAAP Financial Measures The reconciliations of non-GAAP financial measures and non-GAAP ratios for the three months ended June 30, 2026 and June 30, 2025 to the most directly comparable measures calculated in accordance with IFRS are presented below. Total Cash Receipts, Normalized Total Cash Receipts and Total Cash Royalty Receipts Total Cash Receipts refers to Total Cash Royalty Receipts plus cash receipts from all products. Total Cash Receipts includes cash receipts from interest as well as non-recurring cash receipts. Total Cash Royalty Receipts refers to aggregate cash royalty receipts and milestone royalty receipts from our portfolio of royalty assets and forms part of Total Cash Receipts. Because of the lag between when we record royalty income and receive the corresponding cash payments on our royalties and milestones, we believe Total Cash Receipts and Total Cash Royalty Receipts are useful measures when evaluating our operations, as they represent actual cash generated in respect of all royalty assets held during a period. We also present Normalized Total Cash Receipts, which refers to Total Cash Receipts adjusted to remove cash receipts that are not expected to recur in the normal course of our operations. We believe that Normalized Total Cash Receipts will assist readers in evaluating the period-over-period performance of our royalty portfolio since Normalized Total Cash Receipts only includes cash receipts generated by royalties and other amounts payable pursuant to the terms of our royalty assets. There were no adjustments required to normalize cash receipts for the three and six months ended June 30, 2026 and 2025. Three months ended Six months ended (thousands of U.S. dollars) June 30, 2026 June 30, 2025 June 30, 2026 June 30, 2025 Total income 50,077 44,130 98,721 88,158 [−] Other interest income (188) (356) (411) (654) [−] Net (gain) loss on marketable securities -- 115 (168) (1,420) [+] Royalties receivable, beginning of period 54,306 45,006 59,708 62,362 [−] Royalties receivable, end of period (54,723) (49,647) (54,723) (49,647) [+] Financial royalty assets, beginning of period 53,930 55,088 57,276 57,527 [−] Financial royalty assets, end of period (55,592) (54,184) (55,592) (54,184) [−] Non-cash royalty income 1 (1,355) -- -- -- [=] Total Cash Receipts, Royalty Cash Receipts and Normalized Cash Receipts 46,455 40,152 104,811 102,142 _______________________________________ 1 Non-cash royalty income relates to Eylea I&II royalties that were deposited into an escrow account but had not yet been transferred to the operation account as of March 31, 2026. The royalties were received on June 4, 2026. Adjusted EBITDA and Adjusted EBITDA Margin We believe Adjusted EBITDA provides meaningful information about our operating cash flows as it eliminates the effects of other noncash expenses and accruals and income and expenses not expected to recur that have been recorded on the interim condensed consolidated statements of net earnings (loss) and comprehensive earnings (loss). We refer to EBITDA when reconciling our net earnings (loss) and comprehensive earnings (loss) to Adjusted EBITDA, but we do not use EBITDA as a measure of our performance. We believe that Adjusted EBITDA Margin is a useful supplemental measure to demonstrate the operating efficiency of our business on a cash basis. Three months ended Six months ended (thousands of U.S. dollars) June 30, 2026 June 30, 2025 June 30, 2026 June 30, 2025 Comprehensive earnings (loss) 7,536 (700) 7,995 (2,532) [+] Amortization of intangible royalty assets 25,464 24,751 50,412 49,496 [+] Depreciation of fixed assets and other intangible assets 1 89 -- 177 -- [+] Income tax expense 3,031 -- 2,628 -- [−] Other interest income (188) (356) (411) (654) [+] Interest expense 9,257 9,028 19,662 18,635 [=] EBITDA 45,189 32,723 80,463 64,945 [+] Royalties receivable, beginning of period 54,306 45,006 59,708 62,362 [−] Royalties receivable, end of period (54,723) (49,647) (54,723) (49,647) [−] Performance fees payable, beginning of period -- (2,198) -- (1,665) [+] Performance fees payable, end of period -- -- -- -- [+] Financial royalty assets, beginning of period 53,930 55,088 57,276 57,527 [−] Financial royalty assets, end of period (55,592) (54,184) (55,592) (54,184) [+] Unrealized (gain) loss on marketable securities 2 -- 115 1,261 (1,420) [+] Unit-based compensation 605 970 1,273 1,430 [+] Board of trustees' unit-based compensation 3 201 452 567 556 [+] (Gain) loss on debt refinancing -- 971 9,794 971 [−] Net (gain) loss on foreign exchange remeasurement (1,603) -- (3,267) -- [+] Net unrealized (gain) loss on derivative instruments 251 1,076 (1,445) 1,156 [=] Adjusted EBITDA 42,564 30,372 95,315 82,031 [÷] Normalized Total Cash Receipts 46,455 40,152 104,811 102,142 [=] Adjusted EBITDA Margin 92 % 76 % 91 % 80 % _______________________________________ 1 Included in general and administrative expenses are non-cash expenses related to the depreciation of fixed assets and amortization of other intangible assets. 2 Unrealized gain (loss) on marketable securities is related to the changes in fair value of the marketable securities prior to realizing gains/losses upon disposition. 3 Certain members of the board of trustees of DRI Healthcare elected to be compensated fully or partially in Deferred Units ("DUs") under DRI Healthcare's Omnibus Equity Incentive Plan, as described on page 12 of DRI Healthcare's second quarter 2026 MD&A. Adjusted Cash Earnings per Unit We believe that Adjusted Cash Earnings per Unit provides meaningful information about our performance as it provides a measure of the cash generated by our assets on a per Unit basis, excluding cash earnings that are not expected to recur. The calculation of Adjusted Cash Earnings per Unit is presented below. Three months ended Six months ended (thousands of U.S. dollars, except per Unit amounts) June 30, 2026 June 30, 2025 June 30, 2026 June 30, 2025 Comprehensive earnings (loss) 7,536 (700) 7,995 (2,532) [+] Amortization of intangible royalty assets 25,464 24,751 50,412 49,496 [+] Depreciation of fixed assets and other intangible assets 1 89 -- 177 -- [+] Unrealized (gain) loss on marketable securities 2 -- 115 1,261 (1,420) [+] Unit-based compensation 605 970 1,273 1,430 [+] Board of trustees' unit-based compensation 3 201 452 567 556 [−] Change in fair value of financial royalty assets (1,662) 904 (3,316) (1,657) [+] Cash receipts on financial royalty assets -- -- 5,000 5,000 [+] (Gain) loss on debt refinancing -- 971 9,794 971 [−] Net (gain) loss on foreign exchange remeasurement (1,603) -- (3,267) -- [+] Net unrealized (gain) loss on derivative instruments 251 1,076 (1,445) 1,156 [=] Adjusted Cash Earnings (Loss) 30,881 28,539 68,451 53,000 Adjusted Cash Earnings (Loss) per Unit – basic 0.56 0.51 1.24 0.95 Adjusted Cash Earnings (Loss) per Unit – diluted 0.56 0.51 1.24 0.95 Weighted average number of Units – basic 55,007,167 55,685,363 55,023,166 55,743,876 Weighted average number of Units – diluted 55,374,923 55,685,363 55,244,232 55,743,876 ______________________________________ 1 Included in general and administrative expenses are non-cash expenses related to the depreciation of fixed assets and amortization of other intangible assets. 2 Unrealized gain (loss) on marketable securities is related to the changes in fair value of the marketable securities prior to realizing gains/losses upon disposition. 3 Certain members of the board of trustees of DRI Healthcare elected to be compensated fully or partially in DUs under DRI Healthcare's Omnibus Equity Incentive Plan, as described on page 12 of DRI Healthcare's second quarter 2026 MD&A. About DRI Healthcare DRI Healthcare is a pioneer in global pharmaceutical royalty monetization. Since our founding in 1989, we have deployed more than $3.0 billion, acquiring more than 75 royalties on 50-plus drugs, including Ekterly, Eylea, Keytruda, Lumvoa (veligrotug), Orserdu, Remicade, Spinraza, Stelara, Vonjo and Zytiga. DRI Healthcare's units are listed and trade on the Toronto Stock Exchange in Canadian dollars under the symbol "DHT.UN" and in U.S. dollars under the symbol "DHT.U". To learn more, visit drihealthcare.com or follow us on LinkedIn . Caution concerning forward-looking statements This news release may contain forward-looking information within the meaning of applicable securities legislation. Forward-looking information can generally be identified by the use of words such as "expect", "continue", "anticipate", "intend", "aim", "plan", "believe", "budget", "estimate", "forecast", "foresee", "close to", "target" or negative versions thereof and similar expressions. Some of the specific forward-looking information in this news release may include, among other things, statements regarding the timing and receipt of the put price, DRI Healthcare's ability to execute on its strategy, the potential and timing of royalty payments, and the anticipated royalty income and anticipated sales of the products underlying such royalties. Forward-looking information is based on a number of assumptions and is subject to a number of risks and uncertainties, many of which are beyond DRI Healthcare's control that could cause actual results to differ materially from those that are disclosed in or implied by such forward-looking information. These risks and uncertainties include, but are not limited to, those risks and uncertainties that are disclosed in DRI Healthcare's most recent annual information form and under "Risk Factors" in DRI Healthcare's Management's Discussion and Analysis. The anticipated royalty terms for products in our portfolio may be shorter than the period of patent protection for the applicable product, depending on many factors, including the entry of generic drugs into the marketplace and competition, all of which are outside our control. No assurance can be given that these are all the factors that could cause actual results to vary materially from the forward-looking statements in this news release. You should not put undue reliance on forward-looking statements. No assurances can be given that any of the events anticipated by the forward-looking statements will transpire or occur, or if any of them do occur, the actual results, performance or achievements of DRI Healthcare could differ materially from the results expressed in, or implied by, any forward-looking statements. Certain assumptions underlying the forward-looking information in this news release include: DRI Healthcare's assumptions regarding demand and growth in pharmaceutical sales, R&D and opportunities for royalty investing; the competitive environment in which DRI Healthcare operates; DRI Healthcare's ability to implement its growth strategies; DRI Healthcare's ability to obtain financing and maintain its existing financing on acceptable terms; DRI Healthcare's ability to maintain good business relationships with marketers and other industry partners; timely receipt of cash royalty receipts; expectations regarding the duration of royalties; DRI Healthcare's ability to keep pace with changing consumer preferences; the absence of material adverse changes in DRI Healthcare's industry or the global economy; currency exchange and interest rates; the impact of competition; the changes and trends in DRI Healthcare's industry or the global economy; and stability in laws, rules, regulations and global standards in the pharmaceutical industry. All forward-looking information in this news release speaks as of the date of this news release. DRI Healthcare does not undertake to update any such forward-looking information whether as a result of new information, future events or otherwise except as required by law. Additional information about these assumptions and risks and uncertainties is contained in DRI Healthcare's filings with securities regulators, including its latest annual information form and Management's Discussion and Analysis. These filings are also available at DRI Healthcare's website at drihealthcare.com/investors . For further information, please contact: Bill Zhang Head of Investor Relations ir@drihealthcare.com SOURCE DRI Healthcare Trust

把神经信号想象成电流，髓鞘就是包裹“电线”的绝缘层。它由大脑里的“髓鞘工厂”——少突胶质细胞制造，主要成分是一种叫 PLP1 的蛋白。 有一群孩子，从出生起，大脑就无法生成足够的绝缘层，即存在髓鞘形成障碍，神经信号传导变得缓慢、紊乱，运动发育明显落后于同龄人。这种病叫佩梅病（Pelizaeus-Merzbacher Disease，PMD），一个在“罕见病”中也不算常见的名字。2020 年11 月，罕见病科普公益平台豌豆Sir公众号与国内佩梅病领域临床诊断与科研经验最丰富的北京大学第一医院儿科教授王静敏医生合作，撰写发表了专题科普（佩梅病：美丽名字背后的魔鬼｜医者仁心）让这种超罕见病被更多人了解，但国内熟悉佩梅病病理机制且具有诊断经验的儿科医生较少，仍然存在不少对佩梅病患者的误诊或诊断延迟案例，患者家庭也普遍缺乏治疗希望。 过去很长一段时间，佩梅病被贴上“无药可医”的标签。但 2025 年 6 月发表在国际科学期刊《Brain & Development》上的一篇权威综述论文《Molecular pathology and treatment strategies in Pelizaeus-Merzbacher disease》，给出了不一样的答案：随着分子病理机制被逐一破解，针对不同类型佩梅病的药物，正从实验室走向临床试验——作者写道，“预期佩梅病在不久的将来成为一种可治疗的疾病，并非过于乐观。” 这篇综述出自日本国立精神·神经医疗研究中心（NCNP）医学基因组中心的 Ken Inoue（井上健）教授，他是全球佩梅病研究领域最有发言权的资深学者之一。今天，我们把这篇文章翻译成患者和家属能读懂的语言，讲清楚佩梅病的来龙去脉，以及正在推进的四条治疗路线。 髓鞘形成低下性脑白质营养不良（HLDs）是一组以中枢神经系统髓鞘“造不出来”为特征的疾病，目前已确认超过 25 种、涉及 30 余个致病基因。佩梅病正是这个大家族中最常见、最具代表性的类型。 它的病因很明确：PLP1 基因突变。PLP1 位于 X 染色体（Xq21.1），编码的蛋白脂质蛋白 1 是中枢神经系统髓鞘中含量最丰富的蛋白，约占少突胶质细胞全部髓鞘蛋白的 40%。致病基因PLP1一出错，髓鞘一般就无法正常生成。 患者通常整体发育迟滞，运动能力的获得尤其困难。早期神经系统症状包括： • 眼球震颤——眼球不自主地摆动 • 肌张力低下——身体“软软的”，缺乏力气 • 痉挛——肌肉僵硬 随着病程推进，还会出现共济失调（走路不稳）、肌张力障碍（不自主的异常姿势），后期缓慢恶化。 需要注意的是，佩梅病并非“一种病一个样”——它的严重程度跨度极大：有的孩子出生后即重度受累、几乎无法获得坐立能力；有的患者成年后仍能行走，仅表现为较轻的症状。这种差异的根源，在于突变类型不同。二、同一个基因，四种“坏法” PLP1 基因的突变可以分成四种类型。它们“坏”的方式不同，病情轻重不同，治疗方向也完全不同： 突变类型 通俗理解 病情 核心机制 治疗方向重复/三倍重复 基因“多了一份” 最常见，中重度 PLP1 蛋白过量，在细胞内堆积，毒害少突胶质细胞 抑制基因表达点突变 基因“写错一个字” 最重（先天型） 蛋白折叠错误，内质网应激 + 铁死亡 抑制表达 + 去铁治疗无效突变 基因“缺了/失效” 最轻（SPG2） PLP1 蛋白缺失，髓鞘基本完整 暂无，补充难调控深度内含子突变 “剪接开关”坏了 轻症（HEMS） 剪接异常，PLP1 产量不足 剪接调控 ASO ▎第一种：重复/三倍重复——“基因多了一份” 这是佩梅病最常见的病因。基因本身的编码没有变，但整段 PLP1 多了一份（甚至三份）。研究显示，小鼠的病情随 PLP1 转基因拷贝数增加而加重，说明过量的 PLP1 对少突胶质细胞有毒性，且呈剂量依赖——多一份，坏一分。 为什么会这样？过量的 PLP1 蛋白无法被细胞正常“安排”，堆积在细胞内的内体与内质网中，还和胆固醇“抱团”，导致髓鞘筏组分的错误转运，最终扰乱髓鞘形成，让少突胶质细胞过早死亡。 既然病根是“太多”，治疗思路就是“减量”——抑制 PLP1 基因的表达。 ▎第二种：点突变——“基因写错一个字” 最严重的佩梅病（先天型）多由点突变引起，通常是某个氨基酸被替换。一个字母的差错，导致蛋白无法正确折叠，卡在内质网里出不去。 堆积的错误蛋白触发细胞的内质网应激反应（UPR）。起初这是细胞的自我保护——减少蛋白合成、加强清理；但当应激超出承受能力，UPR 会转向“促凋亡”模式，命令少突胶质细胞自我了断。研究还发现，阻断促凋亡通路并不能完全挽救疾病，说明背后还有其他机制。 2025 年前后的研究给出了新线索：患者来源 iPS 细胞中发现了铁代谢失调与氧化应激，提示一种名为“铁死亡”（ferroptosis）的细胞死亡方式参与其中。令人惊喜的是，使用铁螯合剂去铁酮，在体外多个突变细胞系和体内重度模型（jimpy 小鼠）中都挽救了细胞表型——针对错义突变型佩梅病患者的去铁酮临床研究，已经启动。 ▎第三种：无效突变——“基因缺了/失效” 这类突变（基因缺失、无义、移码等）导致 PLP1 蛋白完全缺失，患者反而处于疾病谱系最轻的一端，常被诊断为佩梅病的等位基因病——痉挛性截瘫 2 型（SPG2）。动物模型也印证：PLP1 敲除小鼠几乎拥有完整的髓鞘和正常寿命。 这类患者有一个容易被忽视的特征：轻微的周围神经病变（其他突变类型没有）。 治疗上，补充疗法迟迟没有开发，原因很现实：外源 PLP1 的量太难精准调控——补少了没用，补多了又会中毒。这个难题至今无人攻克。 ▎第四种：深度内含子突变——“剪接开关”坏了 这是佩梅病家族的最新成员——HEMS（早髓鞘化结构髓鞘形成不足）。突变藏在 PLP1 第 3 内含子的深处，形成特殊的茎环结构，影响了基因的“剪接”环节：本应优先生产的 PLP1 产量不足，与另一剪接变体 DM20 的比例失衡，导致髓鞘关键成分短缺。 好消息是，一种能识别剪接位点的反义寡核苷酸，已在体外与体内恢复异常剪接——正如它在杜氏肌营养不良、脊髓性肌萎缩中被验证的那样。三、治疗曙光：四条路线正在推进 理解了“每种突变各有各的病灶”，治疗就变得有的放矢。目前正在推进的分子疗法主要有四条路线： ▎路线一：ASO 反义寡核苷酸——“给基因装开关” ASO 是一段人工合成的短核苷酸，像一把精准的“钥匙”，能特异性结合目标基因的 mRNA，破坏或改变它的表达。 • 平台已获验证：治疗脊髓性肌萎缩的诺西那生、杜氏肌营养不良的多款药物，都是 ASO 类药物。 • 重复型佩梅病：针对性的 ASO 已进入临床试验，有望在数年内获得结果——这可能是佩梅病迎来的第一个分子疗法。 • 点突变型：同样适用“抑制表达”的思路，是最具前景的策略之一。 • HEMS：调控剪接的 ASO 已在实验室验证有效。 ▎路线二：AAV 基因治疗——“一针注射，长期起效” 把人工设计的 miRNA（能抑制 PLP1）装入腺相关病毒（AAV）载体，通过单次注射完成治疗——相比需要反复给药的 ASO，患者负担更小。 目前该路线处于临床前阶段：携带靶向 PLP1 人工 miRNA 的 AAV，已能减轻模拟重复型佩梅病的小鼠表型，但尚未开展人体临床试验。 ▎路线三：去铁酮——“清除细胞里的铁锈” 针对点突变型佩梅病发现的“铁死亡”机制，铁螯合剂去铁酮能清除细胞中异常累积的铁离子、缓解氧化损伤。 证据链条已经相当完整：体外多个突变型 iPS 来源少突胶质细胞系、体内 jimpy 重度模型均被挽救；针对错义突变型患者的临床研究已启动。这可能是近期最值得期待的临床进展之一。 ▎路线四：干细胞移植——“先行者与未尽之路” 2012 年，全球首例针对 4 名佩梅病患者的神经干细胞移植试验完成，安全性得到验证；但后续随访显示疗效有限，试验未再继续。原因在于人脑的体积与复杂性，植入的干细胞难以像在啮齿动物中那样广泛扩增与迁移。 这条路虽未走通，却为后来的治疗探索积累了宝贵经验。四、为什么说“可治疗”不再遥远？ 把四条路线和四种突变对应起来看，会发现一个令人振奋的图景： • 重复型（最常见）→ ASO 已进临床试验，AAV 紧随其后； • 点突变型（最重）→ ASO 与去铁酮“双线作战”； • HEMS（轻症）→ 剪接调控 ASO 蓄势待发； • 无效突变（最轻）→ 补充疗法尚待突破，但患者本身症状较轻。 正如作者在综述结语中所说，随着这些治疗选项逐步可及，未来需要建立佩梅病的早期检测与群体筛查，让患者在疾病早期就能接受治疗，从而获得更好的预后。 从“无药可医”到“对症下药”，每一步进展，都来自基础研究数十年的积累、医患之间的相互信任，以及全社会的持续投入。五、给患者与家属的实用建议 ① 尽快明确突变类型。 基因检测不仅帮助确诊，更直接决定治疗路线，四种突变对应疗法完全不同。请在有遗传咨询经验的医院完成检测与解读。 ② 关注临床试验动态。  PLP1重复突变型对因治疗ASO新药临床试验、点突变型去铁酮（铁螯合剂）临床研究都在推进中，建议留意国内外最新临床动态（如查看ClinicalTrials.gov ），或咨询主治医生是否适合入组。 ③ 理性看待“治愈”宣传。 目前尚无获批的佩梅病对应治疗类精准疗法，一切以官方公告与医生意见为准。警惕任何“包治”“百分百有效”的承诺。 ④ 加入病友社群，登记随访数据。 佩梅病之家等患者组织持续开展登记与病情跟踪，这些真实世界数据是推动药物研发与政策支持的重要力量。结语 罕见病不罕见，罕见的是被看见。佩梅病的故事，正在从“被看见”走向“被治愈的路上”。 关注孤儿药创汇，我们一起见证更多罕见病迎来对因治疗的拐点。  连接患者、医生、科研 工作者与爱心人士的罕见病研发与成果转化服务平台      让罕见病被看见，被理解、被治愈，让孤儿药不孤单、促研发、助转化 术语速查表 术语 通俗解释 佩梅病（PMD） 髓鞘形成不足性脑白质营养不良中最常见、最具代表性的疾病 PLP1 编码髓鞘主要蛋白的基因，位于 X 染色体 少突胶质细胞 大脑中负责制造髓鞘的细胞 HLD 髓鞘形成不足性脑白质营养不良，一组罕见病 SPG2 痉挛性截瘫 2 型，PLP1 无效突变导致的轻症等位病 HEMS 早髓鞘化结构髓鞘形成不足，PLP1 深度内含子突变导致的轻症变体 ASO 反义寡核苷酸，人工合成的短核苷酸，可调控基因表达与剪接 AAV 腺相关病毒，常用于基因治疗的递送载体 UPR 未折叠蛋白反应，细胞应对内质网应激的保护机制 铁死亡 铁依赖性脂质过氧化驱动的细胞死亡方式 原文信息：Inoue K. Molecular pathology and treatment strategies in Pelizaeus-Merzbacher disease. Brain & Development 47 (2025) 104383。 DOI：10.1016/j.braindev.2025.104383 免责声明：本文基于已发表学术综述进行科普改写，仅供信息参考，不构成诊断或治疗建议。具体诊疗方案请咨询专业医生。 推荐拓展阅读： 从"折叠错误"到"髓鞘崩塌"：写给佩梅病患者家庭的综述文献解读版科普 PMD专题综述｜从 PLP1 错误折叠到少突胶质细胞变性：以蛋白稳态为核心的佩梅病框架 PMD专题综述｜佩梅病的分子病理与治疗策略 药创AI综述｜佩梅病（PMD）：一种被低估的脑白质营养不良——从临床表型到分子分型 佩梅病：美丽名字背后的魔鬼｜医者仁心 扫码加入“佩梅病暨少突胶质细胞病”专题ima知识库，查询更多专业文献和科研专家 欢迎关注，凝聚微光，伴您同行，让罕见病被看见，让遗传病被理解，让孤儿药不孤单 罕见病科研公益基金推介 汇聚社会爱心 搭建科研与公益的桥梁 2025年2月28日，在深圳市民政局的指导下，深圳市慈善会联合深圳湾实验室科技基金会、深圳医学科学院－深圳湾实验室（SMART-SZBL）罕见病研究中心共同发起“微光同行”公益计划，依托科研单位的专业优势，集中力量攻坚遗传性神经发育罕见病，致力于改善部分罕见病无药可治的现状，通过搭建公益平台、链接多方资源，引导更多社会力量参与推动罕见病科研与公益慈善事业的协同发展。 据悉，2025年度“微光同行”公益计划通过腾讯公益平台等线上线下渠道共募集公众善款约70万元。这笔资金作为“种子资金”，已部分用于资助深圳医学科学院－深圳湾实验室罕见病研究中心的科研项目，重点投向项目启动、早期验证、关键技术突破及合作网络建设等环节，并与深圳医学科学院-深圳湾实验室罕见病研究中心自有经费协同发力，在四大领域实现罕见病系统性推进与关键突破。其余资金正严格按照去年既定的支持科研计划，稳步、有序地执行与落地，确保持续为科研创新注入动能。 科研攻坚多点突破 四大领域迎来曙光 在深圳市慈善会的资源链接与推动下，依托深圳医学科学院与深圳湾实验室的科研优势，“微光同行”公益计划在神经疾病、代谢疾病、罕见肿瘤、肌肉疾病四大领域取得系统性进展与关键突破。 神经疾病领域 项目推动渐冻人症（ALS）个性化药物研发进入临床前评估阶段，并成功诊断疑难儿童神经系统病例，探索“老药新用”策略加速治疗可及。 代谢疾病领域 针对我国高发的苯丙酮尿症（PKU），项目成功研发两代口服酶候选药物，动物实验疗效显著，致力于打破我国该领域长期无药可用的困局。 罕见肿瘤领域 针对腹膜假黏液瘤（PMP）的新药PX完成全部临床前研究，并于2025年底成功实现2例患者给药，完成从实验室到临床的关键跨越。 肌肉疾病领域 国际首个工程化细胞外囊泡（EV）递送mRNA治疗杜氏肌营养不良症（DMD）平台进入临床试验，开创安全、可重复的基因治疗新路径。 拓展罕见病关爱新边界 让微光照亮更多角落 站在公益计划启动一周年的新起点上，深圳市慈善会联合深圳湾实验室科技基金会、深圳医学科学院－深圳湾实验室罕见病研究中心，将继续携手各方力量，让罕见病关爱之光照得更远。2026年，项目将进一步拓展公益边界：计划启动“罕见病诊断下县乡”试点，联合地方政府与合作医院，将罕见病精准诊断能力向基层延伸，帮助更多偏远地区的患儿缩短确诊之路；并诚邀知名人士、科研学者、临床专家、患者代表共同担任“微光使者”，以公众倡导、科普传播、政策建言等方式，推动罕见病议题进入更广泛的公共视野。 此外，项目正探索构建更为紧密的“医－患－研”交流机制。计划自2026年春季起，在深圳湾实验室不定期举办小范围的“走进实验室”开放日活动，邀请部分捐赠人、患者代表、临床医生，与实验室及医科院的科学家们面对面交流，倾听病历之外的生活，分享实验室里正在发生的希望。 以上信息来源于深圳市慈善会官方微信公众号文章：《“科技+公益”的深圳样本：“微光同行”罕见病计划取得关键突破》（2026年2月28日） 播放上方视频，了解“孤儿药创汇”，点击下方标签，关注我们，伴您同行 点个「在看」与转发分享，让罕见病更多被看见，被理解，被关注。关注我们，不见不散。