What Is ALSP

Sisters’ Hope Foundation would like to thank https://www.alspinfo.com/ for their research and for being the source of the information below.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare neurological disease caused by an autosomal dominant genetic mutation in the CSF1R gene (colony-stimulating factor 1 receptor).

ALSP was previously known as two diseases: hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). After the discovery of the gene mutation, these two diseases have become known as one entity: ALSP.

ALSP is one of a group of adult-onset leukodystrophy disorders. Because it is a rare disease, the actual number of cases are unknown.

Symptoms of ALSP

*Courtesy of ALSPinfo.com

Everyone’s journey with ALSP is different. ALSP can present with different symptoms within the same family. The course of ALSP can range from 2 to over 30 years.

ALSP is a progressive disease that is characterized by issues with judgment, personality and psychological changes, and problems with movement.

It is important for people with ALSP to build a support system including family, friends, caregivers, advocacy organizations, and medical professionals to help navigate their symptoms and improve their quality of life.

Symptoms often begin with mild psychological changes and eventually develop into loss of movement and overall function. Early signs of ALSP can be very hard to distinguish from other neurological disorders. These symptoms usually include poor judgment, depression, personality changes, and limited movement problems. As ALSP progresses, the disease can lead to mental decline, severe depression, apathy, anxiety, irritability, and dementia.

Symptoms Checker

Advanced Symptoms

Other symptoms of advanced ALSP include problems sensing vibration, body position, touch, and pain. Some individuals may also have seizures.

Because ALSP is a progressive disease, movement problems will usually develop over time and include Parkinsonian tremor, rigidity, slow movements, and problems sitting or standing. While rare, some people with ALSP may develop stroke-like symptoms and problems with their bones or eyes.

Final stages of ALSP include loss of speech and voluntary motor movement, development of a vegetative state and death. New experimental treatments may help slow or stop the disease.

 

Diagnosis

*Courtesy of ALSPinfo.com

ALSP can progress quickly. Many of the initial symptoms can be misdiagnosed as other neurological disorders.

Symptoms of ALSP can overlap with other neurological conditions, and genetic testing for the CSF1R mutation can confirm an ALSP diagnosis. In addition to genetic testing, an MRI can verify lesions in the brain caused by the loss of myelin, a protective layer for brain cells, around neurons (brain cells). CT scans can detect other abnormal areas in the brain.

*Courtesy of ALSPinfo.com

 

Treatment

There are currently no FDA-approved treatments for ALSP. Those who have it experience a wide range of symptoms. Several existing medications are being used off-label to treat ALSP symptoms. The term “off-label” means the medication is being used in a manner not specified in the FDA’s approved packaging label or insert. Some of these medications include anti-depressants, muscle relaxers, anti-epileptic medications for patients with seizures, and antibiotics for patients that develop pneumonia and urinary tract infections.

Physical therapy may be used to help with movement and muscle problems that result from ALSP. For any genetic disease, psychological and genetic counseling are commonly recommended to cope with mental and physical symptoms as well as the potential risk of inheritance of ALSP in other family members.

In some cases, bone marrow transplants are possible. See Clinical Trials for more details.

ALSP Statistics

 

Clinical Trials for ALSP

Observational – Natural History Study:

Vigil Neuroscience is conducting an observational natural history study with ALSP patients to better understand the disease and help inform the clinical development of VGL101. For more information visit clinical trials.gov HERE.

Join The Natural History Study

If you or a loved one would like to learn more about the studies, please email trials@vigilneuro.com.

 

 

Bone Marrow Transplant:

Masonic Cancer Center, University of Minnesota – Minneapolis, Minnesota https://clinicaltrials.gov/ct2/show/NCT02171104?cond=CSF1R&draw=3&rank=17

Mayo Clinic – Jacksonville, Florida https://clinicaltrials.gov/ct2/show/NCT04503213?cond=CSF1R&draw=2&rank=1

Observational – Patient Registry:

The Myelin Disorders Biorepository Project  https://clinicaltrials.gov/ct2/show/NCT03047369?cond=POLD&draw=4&rank=9

 

Genetic Testing for ALSP

ALSP is a disease caused by a rare mutation in the CSF1R gene on chromosome 5. It is an autosomal dominant disease, meaning that each child born to someone who has the CSF1R gene mutation has a 50% chance of also having this mutation. Because ALSP is often diagnosed after the childbearing years, most individuals have already had children by the time they are aware they have the disease. Currently there is no newborn genetic testing for the CSF1R gene mutation that causes ALSP.

The CSF1R mutation affects cells within the body that are part of the immune system. These cells are called macrophages and microglia. The mutation causes neurons to be misshapen due to the presence of spheroids in part of the cell. Macrophages take myelin away from the misshaped neurons which causes further damage. The CSF1R mutation also leads to underactive microglia, cells that are normally protective for neurons. The combination of neuron spheroids, lack of myelin, and underactive microglia are what cause the symptoms of ALSP.

The Detect Leukodystrophy program is available for patients! The genetic test is free for anyone who may be affected by a leukodystrophy. The patient is responsible for the cost of the Genetic Counselor. Sisters’ Hope Foundation will reimburse the cost of the required genetic counseling. Contact heidi@sistershopefoundation.org for more details. https://www.invitae.com/en/leukodystrophies/

For more information about genetic testing, visit the CDC’s page.

CDC Website | Glossary of ALSP Terms

 

Patient Registry

The ALSP patient registry pre-study survey is LIVE!  

Completing this is the first step for patients who want to participate in the Vigil Neuroscience global digital ALSP patient registry. 

At Sisters’ Hope Foundation, we are encouraging ALSP patients and CSF1R carriers to participate in this registry to enable the scientific community to learn more about ALSP, in the hope that the results will provide information to improve future treatment.  

The full ALSP registry study will be live by the end of this year in the United States and early in 2022 in other countries.  

You can start engaging now by completing this pre-survey at https://alspregistry.com.