Fighting Neurodegenerative Diseases: The Need for Combination Biologics

The small-molecule drug Relyvrio (sodium phenylbutyrate and taurursodiol) was one of the few approved medications for amyotrophic lateral sclerosis (ALS) before it was removed from the shelves in early 2024 after poor phase 3 results. ALS patients have few treatment options now, most of which merely manage the symptoms of the disease without preventing or treating it.

ALS is a rare disease, and in most cases, we don’t know what causes it. The ALS Association determined that about 90% of cases occur without any known family history or genetic cause (1). About 5000 people in the United States are diagnosed with ALS every year, and more than 20,000 Americans live with the disease.

Therapeutics for neurodegenerative diseases currently focus on managing symptoms and improving quality of life for patients. Although such outcomes are welcome, therapies are expensive and do little to improve life expectancy. Marketed therapies for ALS have shown advancements in reducing symptoms but not in curing disease.

For improved quality of life, patients can undergo breathing care, physical therapy, occupational therapy, speech therapy, nutritional support, and psychological support. But it takes an army of medical professionals to ensure such care for those who are suffering. The two remaining approved medicines — riluzole and edaravone — have little impact on patient decline. Patients suffering from ALS deserve better treatments.

Other neurodegenerative diseases such as frontotemporal dementia (FTD), Alzheimer’s disease, and Parkinson’s disease currently face similar challenges. The Partnership To Fight Chronic Disease estimated that costs related to neurodegenerative disease exceeded US$655 billion in 2020, with medical expenses and economic losses included (2).

Treatments for neurodegenerative diseases often have limited effectiveness, but patients still use them to improve longevity and quality of life. The market for treatment options is expected to continue expanding. A 2020 study by Alzheimer’s Disease International estimated that the global cost of care for dementia was $1.3 trillion in 2015 and is projected to reach $2.8 trillion by 2030 (3). As more people age, the need for better treatment options will grow.

And yet, hope for finding long-term treatments for neurodegenerative diseases has never been greater. A 2021 report by the Alliance for Regenerative Medicine (ARM) indicated that more than 900 neurodegenerative-disease therapies are in development (4). The same report predicts that number to reach more than 3100 by 2026, demonstrating the increasing number of brilliant people who are working to find better solutions for loved ones suffering from such afflictions.

For years, drugs have targeted single pathways and failed to address adequately the complex neurodegenerative diseases with multiple physiological pathways. Combination drug strategies could address multiple aspects of disease cascade simultaneously, also helping to improve the chances of slowing or stopping disease progression. Such strategies echo what developers have accomplished in cancer and viral-disease treatments, which use combination strategies that drastically improve life expectancy for patients. Such strategies expand our therapeutic use and make targeting complex multipathway diseases more attainable.

The work of Stanley Appel and Houston Methodist Hospital showed that regulatory T (T_Regs) cells are dysfunctional in patients with neurodegenerative conditions. Appel’s team discovered that T_Reg dysfunction causes inflammation, leading to oxidative stress that plays an important role in neuronal loss and the underlying pathophysiology of neurodegenerative diseases. Inflammation is an important driver of such diseases, and T_Reg cell biology is the common denominator.

Many companies that target inflammation to treat neurodegenerative disease still focus on a single pathway. But the diseases that they address are complex, multipathway conditions, and it is time that research priorities and hypotheses reflect that reality. My company’s lead asset, COYA 302, targets multiple pathways, enhancing T_Reg function while inhibiting proinflammatory cells in the immune system. By addressing both of those pathways, our therapy should stop neurodegeneration from progressing. Ultimately, complex diseases require multidimensional therapies. Combination approaches are the future for treating neurodegenerative diseases.

References

1 ALS Facts and Statistics. ALS News Today: Pensacola, FL, 2024; https://alsnewstoday.com/als-facts-statistics.

2 Neurodegenerative Disease Costs Exceed $655 Billion a Year in Medical Expenses and Economic Losses. Partnership To Fight Chronic Disease: Washington, DC, 2021; https://www.fightchronicdisease.org/latest-news/neurodegenerative-disease-costs-exceed-655-billion-year-medical-expenses-and-economic.

3 Dementia Statistics. Alzheimer’s Disease International: London, United Kingdom, 2024; https://www.alzint.org/about/dementia-facts-figures/dementia-statistics.

4 Regenerative Medicine in 2021: A Year of Firsts and Records. Alliance for Regenerative Medicine: Washington, DC, 2021; https://alliancerm.org/wp-content/uploads/2021/08/ARM-H1-2021-Report.pdf. 

Howard Berman, PhD, is chairman and CEO of Coya Therapeutics. For inquiries, please contact Kati Waldenburg; [email protected].