by Lauren Taylor from In The Cloud Copy
Pantothenate kinase-associated neurodegeneration or PKAN is a rare, inherited condition in which the affected child experiences progressive degeneration in certain parts of the central nervous system. This results in progressive abnormal and involuntary muscle movements, decreases in muscle tone, and postural disturbances. Patients will also display symptoms of abnormal speech, poor balance, difficulty controlling movements, and more.
Imaging of the brain will show iron accumulation on the brain in these patients. Patients are most often diagnosed after an abnormal finding on an MRI, referred to as the “eye-of-the-tiger” sign. Diagnosis is made by genetic testing. There are no promising therapies or treatments for this condition, and patients typically succumb to the disease in childhood or early adulthood, though there are rare cases in which symptom progression plateaus and the patient may live later into adulthood.
Study on Use of Pantethine as Treatment in Children with PKAN
Pantethine is a drug currently marketed for the treatment of hyperlipidemia, but mouse models showed that it could be effective in other areas as well, including restoring mitochondrial dysfunction, increasing levels of CoA in the tissues, and aiding in recovery of neuromuscular phenotypes.
Participants in the study were aged 3-16 years of age who all displayed progressive dystonia. All patients had the classic “eye-of-the-tiger” on brain MRI, and all had pathogenic variants in PANK2. The study was a 24-week study approved by the Ethics Committee of the Peking University First Hospital.
Study participants received the pantethine via oral administration for a 24-week period. The dose was started at 20 mg/kg per day and eventually increased to 60mg/kg where it was maintained throughout the course of the study. Follow up was performed via phone weekly to check in on any adverse events in the first 5 weeks of the study and patients were seen in person at weeks 12 and 24.
Patients were also scored on the Unified Parkinson’s Disease Rating Scale I-III (UPDRS I-III) and the Fahn-Marsden Scale (FM). These scores were taken 24 weeks before treatment. At baseline, researchers took the UPDRS I-III and FM scores, as well as Pediatric Quality of Life Inventory (PedsQL) and activities of daily living (ADL) scores, as well as serum CoA levels, and videos of motion of the patients. The FM and UPDRS I-III were re-scaled at week 12 and the PedsQL, ADLs, clinical impression evaluations, and blinded videos were re-scaled at week 24.
Results of The Study
The rates of increase in the score of the UPDRS I-III and FM scores were slowed fairly significantly after the treatment when compared to scores taken 24 weeks before treatment, indicating that the pantethine may work to slow down the progression of motor dysfunction in these patients.
The parental clinical impression score is a subjective assessment by the guardian or parent of the child. 3/15 parents rated their child as “slightly improved”, “no change” in three, “slightly deteriorated” in seven, and “markedly worse” in two parents. The videos of motor action viewed and rated by neurologists were comparable to what the parental clinical impressions were.
The ADL scale saw no change between weeks 0 and 24, while the quality of life scores did increase for family members, but there was no change in quality of life in the patient. There was no significant change in the serum CoA levels at week 0 and 24.
There were no significant safety events during the 24-week study. Patients tolerated the medication well and liver and renal function were monitored routinely throughout the study’s duration via blood tests.
While the pantethine did not improve motor function as originally hoped, it was found that it could slow down or delay motor dysfunction progression, as four children did show slight improvements. These children did have lower scores on the UPDRS I-III and FM scales at baseline, so it is possible that patients with milder motor handicaps at baseline are more likely to benefit in this area than those that with more advanced handicaps.
While there is no promising treatment for PKAN yet, researchers will continue their efforts to find a treatment to help slow the progression of this devastating disease.
Click here to learn more about this study.