Antibody Therapies Against TDP-43 Protein Clumps Focus of Research
BioArctic AB announced that it is advancing work into selective antibodies against TAR DNA-binding protein 43 (TDP-43) that when misfolded can form the toxic clumps, or aggregates, believed to be involved in the development of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders.
One potential therapy approach is called the ND3014 project and early research into it is underway, the company, based in Sweden, reported.
“BioArctic’s scientists work in a systematic way to identify new methods to address neurodegenerative diseases,” Gunilla Oswald, BioArctic CEO said in a press release. “As the understanding of the underlying causes of ALS has increased, we have found an opportunity to develop new selective antibodies against TDP-43, the protein that plays a key role in the disease progression.”
Although the exact biological mechanisms that cause ALS are not fully understood, one common feature of the disease is the abnormal function of the protein TDP-43.
TDP-43 protein aggregates have been found within cells of the central nervous system — defined by the brain and spinal cord — of ALS patients. These toxic aggregates are believed to cause the degeneration of motor neurons, the nerve cells directly involved with muscle movement, seen in ALS.
TDP-43 clumps have also been found in people with frontotemporal dementia and Alzheimer’s, the company noted.
Current ALS treatments are focused on improving patients’ quality of life by slowing disease progression or relieving its symptoms.
By developing antibodies against TDP-43, BioArctic hopes to lower the levels of toxic TDP-43 aggregates within nerve cells to possibly “achieve a disease-modifying effect,” it stated in the release. Potential antibody-based therapies might stop or significantly delay disease progression for ALS patients, and those with various other neurodegenerative disorders.
“In time, we hope that our work will lead to new treatments that improve the life of these patients and their loved ones,” Oswald said.
The TDP-43 protein typically is involved in the production of other proteins through the regulation of messenger RNA (mRNA), the intermediary product between DNA and a protein, in the cell nucleus. When the gene providing instructions for making TDP-43 is mutated, the resulting protein has an abnormal shape that makes it more prone to accumulate outside the nucleus in the cytoplasm and to clump together.
Mutations in the TARDBP gene are found in people with both sporadic and familial forms of ALS, scientists have reported, calling the resulting clumps of the TDP-43 protein a “defining pathological hallmark found in most ALS patients.”