Hopes and Justification for Research into Genetic Disorders

The cost of US health care is about 17% of GDP and it is expected that there will be 35 million hospital admissions in 2017. In 2004, 133 million Americans lived with a chronic disease. Cost and suffering support aggressive research into prevention and treatment of infections, accidents and disorders. Three conditions — heart disease, cancer, and stroke — total 63.6% of all deaths, and genetic disorders are often the cause or contribute to those conditions. Medical research is aimed toward patient clusters where it can deliver the most benefit. That research is spread across bacterial and viral infections, superior techniques and devices for repairing damaged bodies, and effective ways to change risky behaviors.

Recently, genetic research and the evidence of its success with genetic treatments have rekindled the hopes of millions of Americans who have one or more of the surprisingly broad spectrum of disorders with genetic roots. For example, Autism, breast cancer, colon cancer, Parkinson’s disease, prostate cancer and skin cancer, plus more than a thousand rare disorders, have genetic roots.

The presence of a genetic flaw does not automatically cause a disorder. A study to clarify the relationship between mutations and disorder incidence was undertaken by Stanford University School of Medicine and Fox Chase Cancer Center in Philadelphia. They analyzed genetic test results, family histories and disease status of nearly 95,600 women who underwent genetic testing for 25 mutations associated with the development of breast and ovarian cancer. Some of the women had cancer, but many did not. Seven percent of the women in the study carried at least one of the mutations.

Pursuing research on inherited disorders makes sense, but two-thirds of genetic disorders are not inherited from parents, rather the disorders come from mutations that occur randomly. Knowing the disorder incidence related to each genetic flaw helps researchers determine where to invest their research assets. Knowing the likelihood of developing a disorder also informs patients about the actual level of risk they face and it reduces unnecessary anxiety.

Sometimes research is focused on a specific disorder. Alzheimers Disease (ALZ) causes dementia that develops progressively after age 60. About 5.4 million Americans have Alzheimer disease, costing the US $100 billion per year. Alz patient brains show plaques that are a buildup of amyloid-beta proteins and in later development they show tangles (dying nerve cells). By the time plaques and tangle appear, it is too late to prevent Alz. Late onset Alz (symptoms at age 60 or later) is thought to be caused by several unhealthful lifestyle factors (smoking, obesity, etc.) or a genetic flaw. One genetic factor leading to late onset Alz is the E (APOE) gene on chromosome 19.

A recent CBS story revealed a Columbian family plagued by early onset Alz. The Columbian family had a long-standing history of early Alz. The disorder first appears as dementia after age 30 and few of those afflicted lived after age 50. Researchers used church records to identify the family’s genetic tree back for several hundred years, allowing them to identify first person in the family who had the problem. Researchers tracked the problem to a specific flaw on chromosome 14 that leads to this particularly early onset Alz.

Columbian parents with the flawed gene give their child a 50:50 chance of developing the disorder. To know for sure which people have the flaw (and who will develop early onset Alz), researchers use a DNA test. Advance knowledge of who will and will not develop the disorder provides an unusually strong opportunity to conduct trials in which prospective treatments will be effective in preventing the disorder.

To conduct such a trial, researchers enlist healthy family members before they exhibit tell-tale dementia. A DNA test then identifies those with a flawed chromosome 14 and who will develop Alz. Neither trial subjects nor clinicians running the trial are told of the DNA results. All subjects are given treatment that looks the same but those with the flawed gene get the investigational treatment and the others get a placebo treatment. In 2022, the health status of trial subjects and the efficacy of investigational treatments will be assessed.

Further trials may follow for this group. This trial may be helpful for treatment of other variants of early onset Alz, or even late onset Alz, or, tragically, none of those. Past studies of prospective Alz treatments have experienced failure rates of about 99%.

The time needed for such trials and the costs for monitoring the health and compliance of test subjects weigh heavily on the finances for medical research. Nevertheless, the humanitarian and financial payoffs can justify well-targeted research. Smart choices in today’s research must be viewed as a substitute for costs for tomorrow’s treatment.

FacebooktwitterredditlinkedinFacebooktwitterredditlinkedin