What is ALSP?

What are the symptoms of ALSP?

ALSP is a progressive genetic neurodegenerative disease that is ultimately terminal. Symptoms tend to overlap with conditions like Parkinson's Disease, Alzheimer's Disease and other forms of dementia, multiple sclerosis, schizophrenia, and other conditions with different causes and treatments (2, 6). The average age of diagnosis for those with ALSP is 43 and symptoms have been recorded as early as 18 years old, which contrasts with the later age of onset for some of the overlapping neurodegenerative conditions (7). In fact, 95% of ALSP patients have symptoms before they are 60 years old (2). ALSP can only be confirmed with genetic testing, which makes it particularly important to ensure the correct diagnosis is made. 

The progression of ALSP to the final stages of the disease can be anywhere from 2 years to upwards of 30 years. Initial symptom presentation begins with changes in the following: 

1. Cognition: forgetfulness, poor attention, difficulty problem solving, and others 

2. Psychological State: depression, anxiety, apathy, irritability, cravings, and others 

3. Motor Function: difficulty with walking, or moving more slowly than usual (2, 6). 

Utilize the ALSP Symptom Checker from ALSPInfo.com here: https://alspinfo.com/wp-content/uploads/2021/09/symptom-checker.pdf  

Learn more about the symptoms and progression of ALSP here: https://sistershopefoundation.org/signs-symptoms/  

What Causes ALSP?

ALSP is an Autosomal Dominant genetic condition that can be inherited by either parent or can occur spontaneously with a new genetic change that occurs before birth; only one copy of the disease-causing genetic change is needed to cause the disease (2, 7). This means that parents, siblings, and children of those with ALSP have a 50% chance of also having inherited the condition (7). 

Before the genetic change that causes ALSP was identified, ALSP was classified as two separate conditions (2, 7): 

• HDLS: Hereditary Diffuse Leukoencephalopathy with Spheroids 

• POLD: Pigmentary Orthochromatic Leukodystrophy 

Thanks to research in genetics, the genetic change that causes ALSP was identified within the gene CSF1R (1, 2). CSF1R is a gene named for the receptor it carries the instructions to produce: Colony-Stimulating Factor 1 Receptor. This receptor is responsible for the overall activation of CSF-1 molecules, which are a key part of controlling many cellular processes, like cell growth and differentiation of cells into more specified cellular roles (3). 

The symptoms are caused by lesions that form in the brain and break down white matter, which is critical for proper neurological function. Nerve cells are covered by a myelin sheath, which is composed of white matter, so when it is destroyed in ALSP patients, the neuron loses the ability to send signals appropriately to other nerve cells (2, 7). There are additional impacts of the genetic change that lead to damage or alterations in the function of cells within the nervous system, including the macrophages and microglia critical to healthy immune function (7).

To learn more about the cause of ALSP, visit: https://alspinfo.com/about/  

How is ALSP Diagnosed?

A neurologist is usually the specialist seen to evaluate patients with symptoms of ALSP. Confirmatory genetic testing to identify the altered CSF1R gene is required for definitive diagnosis. Suspicion for diagnosis outside of the presentation of symptoms can also be further investigated through CT or MRI scans, blood tests, or testing of cerebrospinal fluid (CSF) (2).

Genetic testing can determine if someone has a disease-causing copy of the CSF1R gene through a series of analyses that carefully review each of the two versions of the CSF1R gene an individual has inherited from each parent.

This starts with the collection of a saliva, blood, or other laboratory approved DNA sample from the patient followed by a complex sequencing process: 

1. In the lab, chemicals are used to target the specific region of each version of chromosome 5, one from each parent, that contains each of their CSF1R genes (4). 

2. A machine amplifies, or makes numerous copies, of an individual's two CSF1R genes. 

3. Once there are many copies of the DNA, a computer is able to denote small differences between the two versions of the gene and distinguish them as separate; this lets the analyst know if one gene or both are altered. 

4. Each gene version is compared to a known version of a healthy CSF1R gene and known versions of CSF1R genes that have been identified to cause ALSP. 

5. Analysts carefully review scientific studies and literature to determine with the most confidence whether or not any genetic variants within an individual's genes are determined to cause a disease. 

6. A test report summarizing these findings is sent to the genetic counselor for interpretation: sometimes the diagnosis is clear, but other times there are results with unknown health impacts. 

7. The genetic counselor will discuss the test results with the individual to help them understand exactly what the results mean for their health and the health of their family members. This can include providing support resources, other wellness services, or referral to additional providers. 

8. The doctor reviews the test results along with the genetic counselor's interpretation of the results and consultation notes to provide additional diagnostic review, recommendations for treatment, and symptom management.

How is ALSP Treated? 

ALSP currently has no FDA treatments, but there are some medications being used off label for treatment of symptoms.
Some options for care management can include (6, 7): 

• Antidepressants 

• Antiepileptics 

• Muscle relaxers 

• Physical therapy 

• Psychological counseling 

• Genetic counseling 

• Bone marrow transplants 

• Clinical trials

Partnering to Improve Life for those Impacted by
Adult-onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP)

What is Sisters' Hope Foundation?

Sisters' Hope Foundation was founded by Heidi Edwards, the organization's president. Her family's journey with ALSP began over 20 years ago when first Heidi's Aunt, then Mother, and later her Uncle each developed symptoms of a similar disease misdiagnosed as dementia that was both progressive and terminal for each of them. Shortly after Heidi's Uncle passed away, neurologists at the University of Pennsylvania identified the genetic change that had caused the disease for her three late family members and provided a post-mortem diagnosis of ALSP. Having been counseled that the direct family members had a 50% chance of inheriting the same condition, Heidi decided to undergo testing while her other two sisters did not (5). 

While Heidi was negative for the condition, it was in 2019 that both her twin sister Holly and her sister Heather became symptomatic for ALSP. Heather passed away in August 2020. Heidi founded Sisters' Hope Foundation while acting as caregiver for her twin sister with the aims of ensuring that other families experiencing similar tragedies know they are not alone and can gain life changing access to support (5). Holly passed away in July 2021. Sister's Hope Foundation aims to support and empower families impacted by ALSP through four core missions: awareness, advocacy, community, and financial assistance. 

Learn more about Heidi's Journey here: https://sistershopefoundation.org/our-story/  

Learn more about Sisters' Hope Foundation's vision here: https://sistershopefoundation.org/our-mission-vision/ 

How can Clover Genetics Help?

Clover Genetics is focused on improving access to holistic healthcare by providing telehealth genetic counseling and wellness services to patients and families across the United States and its territories. Clover Genetics has partnered with Sisters' Hope Foundation to provide genetic counseling consultations and genetic testing facilitation when appropriate.

Through this program, patient's pre-approved by Sisters' Hope Foundation will be provided a code to utilize as payment. This allows Sisters' Hope Foundation to provide direct financial support to those seeking support for ALSP while removing the financial barrier to care.

Because ALSP is so rare, Clover Genetics has also trained their genetic counselors to provide specialized consultations to address this specific patient population and have confidence in the recommendations provided. Outside of ALSP, Clover Genetics is dedicated to providing the highest level of personalized and holistic care and offers support to patients throughout the entire process. 

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Learn more about Clover Genetics' vision here: http://clovergenetics.com/about-us