Rushing to the Cure for Alzheimer's: A Discussion of Pharmaceutical Methods vs. Gene Therapy

Rushing to the Cure for Alzheimer's: A Discussion of Pharmaceutical Methods vs. Gene Therapy

Alzheimer’s disease is reported as the 6th leading cause of death in the U.S. with currently 5.7 million of affected Americans. This number is expected to rise to 14 million by the year 2050, according to the Alzheimer's Association. With the numbers quickly increasing, research interest has also increased due to the unmet need for a cure. However, a fundamental question remains. What will be the “best” treatment for the disease?

The article, Despite Setbacks, Drugmakers Have Plans to Fight Alzheimer’s, published in The Wall Street Journal, described the plans of several research groups in the pharmaceutical industry. With growing concern, funding for Alzheimer’s disease has nearly tripled since 2013; however, many scientists do not guarantee any ground-breaking progress in the short term. For several years, the pharmaceutical industry has focused on the aspect of dementia in Alzheimer’s, but reversing brain damage is very difficult.

Many researchers in this field believe that beta-amyloid/amyloid plaque leads to the development of Alzheimer’s disease. The heavy focus on the late effects of Alzheimer’s prompted scientists to target amyloid plaque with drugs (solanezumab) but resulted in nonsignificant effects on cognition. Nevertheless, scientists shifted toward catching the disease at earlier stages. Even then, medications like verubecestat which is a BACE inhibitor that prevents enzyme production of amyloid failed to show any benefits. Other drugs like aducanumab, can clear beta-amyloid plaque, but also produce adverse effects. As more pharmaceutical methods are tested, one central conflict persists. The struggle remains in catching the disease early enough for these drugs to work. How early can patients be diagnosed even before prodromal stages?

Dr. Roy (MD. Ph.D.), a neuropathologist and researcher, plans to defeat Alzheimer’s differently. He argues that it may be a product along the pathway of amyloid plaque formation that leads to the disease, rather than the plaque itself.  By using CRISPR/Cas9 methods with gene-therapy, Dr. Roy explained how the Cas9 nucleus cuts specific DNA strands with the help of gRNA (guiding RNA). Essentially, gRNA is a sequence of RNA that is complementary to another sequence in the DNA strand. gRNA forms a complex with the Cas9 nucleus to perform its function. By combining these two components, researchers can direct the enzyme toward a particular point in the DNA and produce functionality analogous to a highly specific designer restriction enzyme. With this in mind, the CRISPR/Cas9 method can alter proteins produced in the genome and truncate the pathway for amyloid plaque production. Therefore, Alzheimer's disease may be prevented due to the inhibition of amyloid plaque production entirely-- all with one injection.

   Whether researchers focus on gene therapy or pharmaceutical methods to treat Alzheimer’s, both concentrations are dealt similar issues. For one, both designs require subjects at earlier stages of the disease, a complex condition to diagnose. Additionally, researchers need more time to test their hypotheses on animal models before even moving into clinical trials. Scientists are setting long-term projects that may take years to complete. Lastly, the cost of these drugs or injections has not been considered yet. Healthcare in America has been a severe societal issue the past few years. If the rate of Alzheimer’s disease cases continues to escalate as projected, government policies should consider regulating the cost of these future treatments. It may be many years until the “best” cure for Alzheimer’s is conceived; however, higher awareness and support from society may expedite the process.

Works Cited

Hernandez, Daniela, et al. “Despite Setbacks, Drugmakers Have Plans to Fight Alzheimer's.” The Wall Street Journal, Dow Jones & Company, 9 Jan. 2018, www.wsj.com/articles/drug-industry-isnt-giving-up-on-alzheimers-1515457652.

Sun, Jichao, and Subhojit Roy. “The Physical Approximation of APP and BACE-1: A Key Event in Alzheimers Disease Pathogenesis.” Developmental Neurobiology, vol. 78, no. 3, 2017, pp. 340–347., doi:10.1002/dneu.22556.