Amanda Twinam’s Journey: Linking Genetic Disorder to Chronic Fatigue Syndrome

Amanda Twinam, a breast cancer survivor and lawyer from Albany, New York, has become the catalyst for a new scientific discovery that may help people suffering from chronically fatiguing illnesses, including long COVID. Twinam’s journey to understand her decades-long fatigue led her to the National Institutes of Health (NIH) where researchers made a groundbreaking finding.

Twinam’s fatigue began with a breast cancer diagnosis at age 28, leading to a mastectomy and chemotherapy. She experienced sickness and seizures as side effects of the treatment. A rheumatologist later found a marker for autoimmune diseases in her blood, but none of the proposed diagnoses fully fit her symptoms. Twinam’s fatigue persisted, leading her to seek further answers.

In 2015, Twinam was diagnosed with Li-Fraumeni syndrome, a genetic cancer disorder. She underwent another mastectomy for a second breast cancer diagnosis, but still felt that something else was wrong. As she entered her 40s, Twinam faced increasing trouble with standing and walking, causing her to scale back to part-time work. Doctors struggled to find a definitive explanation for her symptoms.

Twinam’s persistence and love for biology led her to read a journal article about Li-Fraumeni syndrome and mitochondrial problems. She reached out to Paul Hwang, an NIH researcher who had studied the syndrome, to explore the possibility of her specific version causing a different energy problem. Hwang responded and agreed to investigate further.

After running tests, Hwang discovered that Twinam’s energy problems were not related to Li-Fraumeni syndrome as initially thought. Instead, he found that an excess of a protein called WASF3 was disrupting energy production in Twinam’s cells. This protein jammed up the mitochondria’s supercomplex, causing energy depletion. Further laboratory work confirmed the findings.

This discovery led to a publication in the journal PNAS in August, garnering excitement from researchers in the ME/CFS field. Nine out of 14 ME/CFS patients in a separate study had similar elevated levels of WASF3, suggesting a potential treatment strategy for the widely misunderstood condition. ME/CFS affects up to 2.5 million Americans and is commonly misdiagnosed or delayed.

For Hwang, finding a treatment for ME/CFS is now his motivation. His small laboratory is planning a clinical trial with a drug that recently came on the market for another disease. Twinam believes her story has finally been legitimized, providing validation for the debilitating condition she has faced for so long.

ME/CFS research has suffered from a lack of funding, delayed diagnosis, and a lack of approved treatments. The COVID-19 pandemic has exacerbated the issue, as up to half of long COVID patients meet the criteria for ME/CFS. The hope is that this new scientific discovery will shed light on the mechanisms of the disease and lead to improved treatments and understanding.