Welcome to March!  Just like that we are onto our 9th post in Neural Frontiers.  This week, I’m writing the blog post from my in-laws’ new home in North Carolina.  Thankfully (very very thankfully) I have two In-laws approaching their 70s who are still mentally strong.  However, this week’s post is still a difficult one when I think of so many friends whose families are impacted by the sad realities of neurodegenerative disease.  Parkinson’s and Alzheimer’s are two of the most difficult diseases we can watch loved ones have to endure.  Luckily, we are progressing towards a future where these diseases affect less and less of our loved ones.  It is with hope and optimism that I bring you this week’s look into the neurodegenerative disease landscape. 

The $300B Opportunity in Neurodegenerative Diseases

In the United States alone, the global costs of Alzheimer’s and related dementias will reach $2.8 trillion by 2030. Behind these staggering figures are the stories of 55 million people worldwide currently living with dementia, including 6.7 million Americans suffering from Alzheimer’s disease—a number expected to nearly double to 13 million by 2050 according to the Alzheimer’s Association’s 2024 report.

The convergence of artificial intelligence, advanced neuroscience, and biotechnology creates a perfect storm of innovation in the neurodegenerative disease. With the global neurotech market projected to grow at a CAGR of 13.2% to reach $37.5 billion by 2029, investors and startups are positioning themselves at the frontier of what could become one of healthcare’s most transformative decades. As computational capabilities expand and our understanding of the brain deepens, the gap between scientific discovery and commercial application is narrowing.

Market Gaps and Investment Opportunities

Despite billions invested in traditional drug development, the success rate for neurodegenerative disease treatments remains dismally low, with over 99% of Alzheimer’s clinical trials failing between 2002 and 2022. This extraordinary failure rate stems from the brain’s complexity, limited understanding of disease mechanisms, and the challenge of effectively developing treatments that can cross the blood-brain barrier.

According to data from the Tufts Center for the Study of Drug Development, the average cost to bring a single neurological drug to market now exceeds $2.8 billion, compared to $1.3 billion for drugs in other therapeutic areas. 

These obstacles, however, make the neurotech sector ripe for disruption and investment. The urgent unmet need, combined with scientific advances in multimodal brain imaging, genetic sequencing, and AI-driven target discovery, has created unique market opportunities for companies approaching neurodegeneration from new angles. 

Early diagnosis technologies alone represent a $5.9 billion market by 2028, while disease-modifying therapies could capture a $30+ billion market for Alzheimer’s and $11+ billion for Parkinson’s disease annually, based on recent market research from Grand View Research and GlobalData Healthcare.

Beyond Statistics: Notable Figures Bringing Awareness to Neurodegenerative Diseases

Parkinson’s Disease in the Public Eye

Parkinson’s disease typically progresses silently for years before diagnosis, with patients losing 60-80% of dopamine-producing cells before symptoms become noticeable enough for clinical detection. This diagnostic challenge has significantly hampered early intervention efforts. Michael J. Fox, diagnosed with young-onset Parkinson’s in 1991 at age 29, transformed this landscape when he went public with his diagnosis in 1998 and established The Michael J. Fox Foundation in 2000, which has since funded over $1.5 billion in Parkinson’s research, becoming the largest non-governmental funder of Parkinson’s research globally.

The visibility brought by Fox and the late Muhammad Ali, who battled Parkinson’s for three decades before he died in 2016, has directly translated into capital formation in the Parkinson’s research space. Following Fox’s congressional testimony in 2022, federal funding for Parkinson’s research at the NIH increased by 21% to reach $229 million in 2023. Similarly, venture funding for Parkinson’s-focused startups reached a record $420 million in 2023, a threefold increase from 2018 levels according to PitchBook data, demonstrating how public advocacy directly translates to investment opportunities.

Alzheimer’s Disease Advocacy

Alzheimer’s disease remains surrounded by persistent stigma, with a 2023 Alzheimer’s Association survey finding that 40% of Americans would not tell others if they were experiencing symptoms of cognitive decline. This reluctance to acknowledge the disease hampers clinical trial enrollment and early intervention efforts. Actor and filmmaker Seth Rogen, whose mother-in-law was diagnosed with early-onset Alzheimer’s, launched Hilarity for Charity in 2012, which has raised over $18 million and reached millions of younger Americans previously disengaged from the dementia conversation.

The impact of celebrity advocacy on Alzheimer’s funding is measurable. In the three years following the public disclosure of Tony Bennett’s diagnosis and his final performances with Lady Gaga in 2021, private philanthropic contributions to Alzheimer’s research increased by 35%, according to the American Brain Foundation. 

The 2023 documentary “Bruce Willis: The Legacy,” chronicling the actor’s battle with frontotemporal dementia, led to a 7x increase in visits to educational resources about FTD and a surge in clinical trial enrollment applications, demonstrating how personal stories from beloved figures translate directly into research acceleration potential.

ALS and the Power of Social Media

Amyotrophic Lateral Sclerosis (ALS) affects approximately 30,000 Americans, with 5,000 new diagnoses annually—numbers too small to attract proportionate research funding through traditional channels. The 2014 Ice Bucket Challenge, inspired by former Boston College baseball player Pete Frates, became a viral phenomenon that engaged over 17 million participants worldwide and raised $115 million for the ALS Association in just eight weeks. This unprecedented awareness campaign led directly to discovering five new ALS genes and funded 40 research projects.The late physicist Stephen Hawking, who lived with ALS for 55 years, defying the typical 2-5 year prognosis, brought unparalleled scientific credibility to ALS advocacy. According to CB Insights, after his death in 2018, investment in AI-assisted communication technologies for neurodegenerative patients increased by 62% year-over-year. Project Euphonia, a Google research initiative inspired partly by Hawking’s experience, is now developing voice recognition technology specifically for people with speech impairments from conditions like ALS, creating entirely new markets at the intersection of technology and neurodegenerative care.

Startup Spotlight: Leading the Innovation Wave

Muna Therapeutics

Founded in 2020 through the merger of Teitur Trophics and Axxam’s neurodegeneration portfolio, Muna Therapeutics secured one of Europe’s largest Series A biotech rounds in 2021, raising $73 million led by Novo Holdings with participation from Sofinnova Partners, Droia Ventures, and LSP Dementia Fund. Most recently, the company received $4.9 million of grant funding from Michael J. Fox Foundation on October 11, 2022. The Copenhagen and Leuven-based company is developing small molecule therapies that address the upstream factors triggering neurodegeneration. Their leadership team brings exceptional credentials to the challenge, with CEO Rita Balice-Gordon previously heading Pfizer’s Neuroscience and Pain Research Unit and CSO Anders Hinsby bringing expertise from Orphazyme and Nuevolution.

Muna’s differentiated approach focuses on restoring neuronal function through two key programs that set them apart from competitors. Their lead program targets TREM2 (Triggering Receptor Expressed on Myeloid cells 2), developing agonists that boost the brain’s immune cell function to clear toxic proteins implicated in early-stage Alzheimer’s disease—a mechanism gaining validation through recent clinical successes with antibodies targeting similar pathways. Their second program focuses on blocking Kv1.3 potassium channels to reduce neuroinflammation, which represents a promising approach for slowing disease progression across multiple neurodegenerative conditions. This dual-pronged strategy targeting both clearance and inflammation pathways positions Muna uniquely among companies focused solely on single mechanisms of action.

Other Notable Players

Alector (NASDAQ: ALEC), operating at the intersection of neurology and immunology, has pioneered the emerging field of immuno-neurology with their proprietary platform targeting genetic risk factors for neurodegeneration. Their lead candidate AL001, a TREM2 activator for frontotemporal dementia, has shown promising Phase 2 results with demonstrable reductions in disease biomarkers. With a $310 million collaboration with GSK established in 2021 and a current market capitalization of approximately $730 million, Alector represents the more established end of the neurotech investment spectrum, having successfully translated their scientific approach into clinical-stage assets with significant pharma backing.

Recent Developments Reshaping the Landscape

Strategic Alliances Creating New Value

Muna Therapeutics’ recently announced strategic alliance with GSK in February 2024 represents a significant validation of their approach to Alzheimer’s treatment. The collaboration, valued at up to $632 million including $55 million upfront and additional development and commercial milestone payments, focuses on advancing Muna’s TREM2 agonist program. This partnership follows the industry-wide trend of major pharmaceutical companies returning to neuroscience through biotech partnerships rather than internal programs, with CNS-focused biotech deals increasing 43% in value from 2022 to 2023 according to SVB Securities. For startups in the space, these strategic alliances offer crucial validation, capital efficiency, and commercialization pathways that can significantly de-risk development programs.

Similarly transformative is the August 2024 acquisition of Cerevel Therapeutics by AbbVie for $8.7 billion, representing a premium of over 70% to Cerevel’s pre-announcement trading price. This transaction, focused primarily on Cerevel’s neuroscience pipeline including their M4 agonist for Alzheimer’s psychosis and schizophrenia, signals renewed big pharma confidence in neurodegenerative disease investments following decades of retreat from the space. For the neurotech ecosystem, these large transactions create virtuous cycles of talent, capital, and innovation as founding teams and early investors redeploy resources into new ventures targeting adjacent neurological challenges.

Public Funding Initiatives

The EU Joint Programme – Neurodegenerative Disease Research (JPND) announced its 2025 research call in January, allocating €30 million for health and social care research in neurodegenerative diseases. This initiative, spanning 30 countries and focusing on implementation and scalability of care solutions, creates unique opportunities for startups developing digital health, remote monitoring, and AI-enabled care coordination technologies. Public funding initiatives like JPND are particularly valuable for early-stage companies as they provide non-dilutive capital and clinical validation opportunities through partnerships with academic medical centers.

In the United States, the NIH’s BRAIN Initiative has committed an additional $500 million over five years (2024-2028) to accelerate translation of neurotechnology from lab to market, specifically emphasizing technologies addressing neurodegenerative diseases. The program includes Small Business Innovation Research (SBIR) funding mechanisms with dedicated tracks for neurodegenerative disease technologies that have completed proof-of-concept work. For startups, these initiatives offer not only capital but also access to specialized expertise, patient cohorts, and regulatory guidance that can significantly accelerate development timelines in this notoriously challenging field.

The Road Ahead

Timeline and Milestones to Watch

The neurodegenerative disease landscape is poised for several pivotal developments over the next 24-36 months that will reshape investment opportunities. By Q3 2025, results from Biogen and Eisai’s AHEAD 3-45 trial of lecanemab in pre-symptomatic Alzheimer’s are expected, potentially expanding the addressable market for anti-amyloid therapies from 2 million to 18+ million Americans if proven effective in earlier disease stages. In the Parkinson’s space, Cerevel’s Phase 2 trial of tavapadon, a selective D1/D5 receptor partial agonist, will report full data by mid-2025, potentially validating a more precise approach to dopamine modulation. For early-stage investors, these clinical milestones validate biological pathways that can de-risk investments in startups working on next-generation approaches targeting the exact mechanisms.

Regulatory developments will similarly transform the investable landscape, with the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee scheduled to review updated guidance on digital endpoints for neurological conditions in Q4 2024. According to regulatory experts at the Margolis Center for Health Policy, this guidance is expected to formalize acceptance of remote assessment technologies and digital biomarkers as valid endpoints in registration trials, potentially accelerating approval timelines for neurotech companies by 30-40%. For VCs, these regulatory shifts suggest allocating capital toward startups developing therapeutic assets and complementary digital assessment technologies that could become industry-standard platforms as traditional endpoints evolve.

Investment Criteria for the New Wave

Early-stage investors should prioritize companies demonstrating three key attributes that differentiate successful neurotech ventures from the historical failures in the space. First, look for platforms that account for disease heterogeneity through precision patient stratification via genetic markers, fluid biomarkers, or digital phenotyping. Second, prioritize approaches with opportunities for early proof-of-concept in humans, such as Phase 1b trials with biomarker readouts or medical device studies with objective functional measures. Third, seek capital-efficient development strategies that leverage regulatory accelerations, such as the FDA’s Breakthrough Therapy designation, which has been granted to 70% more CNS therapies in 2023-2024 compared to the previous two-year period.

Growth-stage investors face a different calculus, with opportunities to back companies approaching key value inflection points in the rapidly evolving reimbursement landscape. The Centers for Medicare & Medicaid Services’ 2024 National Coverage Determination for monoclonal antibodies targeting amyloid has created a framework for coverage of disease-modifying therapies with Category B IDEs (Investigation Device Exemptions), extending to novel neuromodulation and drug-device combination products. This framework suggests prioritizing companies with dual therapeutic-diagnostic strategies that can parallel navigate FDA and CMS processes in parallel. The most compelling late-stage investments will combine robust efficacy with implementable, cost-effective solutions for the real-world care delivery challenges that have limited uptake of recently approved therapies despite their scientific breakthroughs.

Why Now is the Time to Invest

The convergence of scientific breakthroughs, regulatory evolution, and unprecedented public awareness has created a unique inflection point in neurodegenerative disease innovation. After decades of disappointment, the first genuinely disease-modifying therapies have reached patients, validating biological pathways and creating blueprints for more effective, accessible next-generation approaches. The FDA’s approval of three Alzheimer’s treatments since 2021 has established regulatory precedents that will accelerate future development timelines, while improvements in biomarker technologies now allow for objective disease monitoring that was impossible just five years ago.

For venture capitalists considering the space, conduct technical due diligence by evaluating whether a company’s approach addresses neuroinflammation, protein aggregation, or neuronal energy metabolism—the three mechanisms with most substantial clinical validation. 

For startups, prioritize partnerships with patient advocacy organizations that can provide clinical trial access and invaluable insights into real-world implementation challenges. 

For neurotech enthusiasts looking to stay informed, resources like the Alzheimer’s Association Research Roundups, The Michael J. Fox Foundation’s Parkinson’s Podcast, and the European Brain Council’s policy briefs provide accessible updates on this rapidly evolving field. 

The companies that will create extraordinary value in this space will combine scientific innovation with patient-centered approaches to overcome the complex challenges that have historically limited progress against these devastating diseases.