Myotonic dystrophy type 1 (DM1), an inherited disease affecting muscles, was one of the first described “expanding repeat” disorders. In these 50…
The Treatabolome Will Shorten Diagnostic Odysseys for Rare Diseases
The journey of naming an odd collection of symptoms is called, for good reason, the diagnostic odyssey. It can take years for gateway health care providers and then sequences of siloed specialists to synthesize clinical findings and a family’s observations into a diagnosis.
Consider Hannah’s Sames’ journey. Hannah had gene therapy for giant axonal neuropathy in 2016, and I tell her story in my book The Forever Fix: Gene Therapy and the Boy Who Saved It. Hannah was diagnosed at age 3; she just attended her junior prom!
The first sign of Hannah’s condition, in retrospect, was her tight curls, the consequence of buildup of an abnormal protein, gigaxonin. The second sign was her odd gait as a toddler. A pediatrician, orthopedist, and podiatrist had no idea that the feathery filaments of abnormal gigaxonin were already distorting the motor neurons whose axons stretched down the little girl’s legs.
Male doctors dismissed the concerns of Hannah’s mother, Lori. It wasn’t until Lori showed cell phone video of Hannah walking to a physical therapist acquaintance that the family was steered onto the diagnostic road towards a neuromuscular disease. By the time a pediatric neurologist recognized Hannah’s condition, the child had just passed her fourth birthday.
Hannah’s prolonged diagnostic experience is not unusual. I’ve written about many children who have undergone gene therapy for rare conditions: the “butterfly-children” who have lost skin due to epidermolysis bullosa, kids who need nightly “bili lights” to treat Crigler-Najjar-syndrome, a teen suffering from sickle cell disease, and kids, like Hannah, with other neurological conditions, such as Sanfilippo syndrome and Batten disease.
So I was excited to read about an initiative from Solve-RD called the Treatabolome project. It’s an online platform to collect and provide treatment information geared to specific genes and gene variants (mutations) to any and all healthcare professionals, not just the specialists brought in as the light at the end of the diagnostic tunnel comes into view.
A special issue of the Journal of Neuromuscular Diseases accompanies announcement of the Treatabolome. It offers literature reviews that sum up the state of our knowledge for a beginning slate of mostly neurological or neuromuscular disorders.
Rare diseases account for about 7 percent of the US population and about 6 percent of Europeans, with mutations behind two-thirds of them. For about a quarter of patients with rare diseases, the diagnostic odyssey is a long and winding road, some up to 30 years, according to Eurordis, “The Voice of Rare Disease Patients in Europe.”
The rare disease community has long sought accelerated diagnoses, but a convergence of advancements – in diagnostics and therapeutics – is finally making that a reality. Consider just one disease, spinal muscular atrophy.
SMA is nearly as prevalent as cystic fibrosis, but from my experience as a genetic counselor, not well known. It is horrific, typically lethal in early childhood. Yet two biotechnologies have made life nearly normal for some kids with SMA: gene therapy and gene silencing, which I wrote about
“The Treatabolome project arises from the improved availability of genetic diagnosis and the rapidly growing number of rare disease treatments. Although targeted treatments are currently only available to a minority of patients with rare diseases, recent developments point towards a steep increase in the coming years, as suggested by the development of multiple gene therapies and the steady increase in the number of orphan drug applications,” said Gisèle Bonne, PhD, of the Sorbonne, guest editor for the special journal issue.
Getting down to the details, the Treatabolome will begin with:
• Genetic forms of Parkinson’s disease and peripheral neuropathies like Hannah’s disease
• Certain rare birth defects
• “Channelopathies” that affect the ions that go in and out of muscle cells
• Muscle disorders arising from glitches in fat metabolism or glycogen storage
• A rare form of muscular dystrophy (facioscapulohumeral)
• Tumor risk syndromes
• Laminopathies, which affect the membranes around cell nuclei
The project plans to include more diseases and to use artificial intelligence to speed analysis of new reports in the medical literature.
“We must strive to work towards a world with progressively fewer ‘undiagnosed’ and ‘not yet diagnosed’ rare disease and ultra-rare disease patients. Most importantly, once a diagnosis is reached, if a treatment exists for the disease/gene/variant, one should not have to wait for it to be offered to the patient,” summed up Dr. Bonne.
It’s been ten years since I wrote The Forever Fix, which detailed many diagnostic odysseys, and twenty years since the first draft of a human genome sequence was published.
But now, the International Rare Diseases Consortium predicts that 1000 new treatments will be available by 2027.
I can’t believe it’s taken this long to shrink the terrible time when parents careen from specialist to specialist, diverted by detours, hope shattered when treatments that work for related conditions prove useless. I hope that the Treatabolome will help the rare disease families of the future get answers, and targeted treatments, much sooner.