'''Tofersen''' is an investigational antisense oligonucleotide designed to treat [[amyotrophic lateral sclerosis]] (ALS) associated with mutations in the [[superoxide dismutase 1]] (SOD1) gene. It is a synthetic molecule that targets the mRNA of the SOD1 gene, aiming to reduce the production of the mutant SOD1 protein, which is implicated in the pathogenesis of ALS.
* Tofersen ('''Qalsody''') is used for the treatment of [[amyotrophic lateral sclerosis]] (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene.
== Mechanism of Action ==
== '''How does this medicine work?''' ==
Tofersen works by binding to the mRNA of the SOD1 gene, which is responsible for encoding the SOD1 protein. By binding to this mRNA, Tofersen promotes its degradation through the recruitment of [[RNase H]], an enzyme that cleaves the RNA strand of RNA-DNA hybrids. This process reduces the levels of SOD1 protein, particularly the mutant forms that are toxic to motor neurons.
* Tofersen is an '''antisense oligonucleotide that causes degradation of SOD1 mRNA through binding to SOD1 mRNA, which results in a reduction of SOD1 protein synthesis.'''
== Clinical Development ==
== '''Who Should Not Use this medicine ?''' ==
Tofersen is currently undergoing clinical trials to evaluate its safety and efficacy in patients with SOD1-ALS. The trials are designed to assess the drug's ability to slow the progression of ALS symptoms and improve motor function. Initial studies have shown promise, with some patients experiencing stabilization of their condition.
* This medicine have no usage limitations.
== Administration ==
== '''What drug interactions can this medicine cause?''' ==
Tofersen is administered via intrathecal injection, which involves delivering the drug directly into the [[cerebrospinal fluid]] (CSF) surrounding the spinal cord. This method of administration is chosen to ensure that the drug reaches the central nervous system, where it can exert its effects on motor neurons.
* Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and [[grapefruit]] you are taking or plan to take.
== Potential Side Effects ==
== '''Is this medicine FDA approved?''' ==
As with any investigational drug, Tofersen may have side effects. Commonly reported side effects include headache, back pain, and procedural pain associated with the intrathecal injection. More serious side effects are being monitored in clinical trials to ensure patient safety.
* Tofersen was approved for medical use in the United States in April 2023.
== Future Directions ==
== '''How should this medicine be used?''' ==
Research is ongoing to determine the long-term efficacy and safety of Tofersen in treating SOD1-ALS. Additionally, studies are being conducted to explore the potential of antisense oligonucleotides in treating other forms of ALS and neurodegenerative diseases.
'''Recommended dosage:'''
== Related Pages ==
* The recommended dosage is '''100 mg (15 mL) of Qalsody per administration'''.
* Initiate Qalsody treatment with 3 loading doses administered at 14 day intervals. A maintenance dose should be administered once every 28 days thereafter.
* If the second loading dose is missed, administer Qalsody as soon as possible, and administer the third loading dose 14 days later.
* If the third loading dose or a maintenance dose is missed, administer Qalsody as soon as possible, and administer the next dose 28 days later.
'''Administration:'''
* [[Amyotrophic lateral sclerosis]]
* Qalsody is supplied as a sterile, preservative-free, clear, and colorless to slightly yellow solution in a Type I glass vial to be administered by intrathecal administration.
* [[Superoxide dismutase 1]]
* Administer Qalsody intrathecally using a [[lumbar puncture]] by, or under the direction of, healthcare professionals experienced in performing lumbar punctures.
* [[Antisense oligonucleotide]]
* Allow to warm to room temperature prior to administration.
* [[Neurodegenerative disease]]
* Administer within 4 hours of removal from vial.
* Prior to administration, remove approximately 10 mL of [[cerebrospinal fluid]].
* Administer as an [[intrathecal]] bolus injection over 1 to 3 minutes.
== '''What are the dosage forms and brand names of this medicine?''' ==
[[Category:Investigational drugs]]
[[Category:Neurology]]
This medicine is available in fallowing doasage form:
[[Category:Genetic disorders]]
* '''As Injection:''' 100 mg/15 mL (6.7 mg/mL) solution in a single-dose vial.
This medicine is available in fallowing brand namesː
* '''Qalsody'''
=='''What side effects can this medication cause?'''==
The most common side effects of this medicine may include:
* Pain
* [[Fatigue]]
* [[Arthralgia]]
* CSF white blood cell increased
* [[Myalgia]]
* CSF protein increased
* [[Musculoskeletal]] stiffness
* [[Neuralgia]]
Less common, but serious side effects may include:
* [[Myelitis]] and/or [[Radiculitis]]
* [[Papilledema]] and Elevated [[Intracranial Pressure]]
* [[Aseptic Meningitis]]
==''' What special precautions should I follow?''' ==
* Inform patients and caregivers that Qalsody could cause [[myelitis]] and [[radiculitis]]. Instruct patients and caregivers to contact their healthcare provider if symptoms consistent with these adverse reactions develop.
* Inform patients and caregivers that Qalsody could cause [[papilledema]] and elevated [[intracranial pressure]]. Instruct patients and caregivers to contact their healthcare provider if symptoms consistent with these adverse reactions develop.
* Inform patients and caregivers that Qalsody could cause [[aseptic meningitis]]. Instruct patients and caregivers to contact their healthcare provider if symptoms consistent with meningitis develop.
* There are no data on the presence of tofersen or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.
== '''What to do in case of emergency/overdose?''' ==
* {{overdose}}
== '''Can this medicine be used in pregnancy?''' ==
* There are no adequate data on developmental risks associated with the use of Qalsody in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
=='''Can this medicine be used in children?'''==
* Safety and effectiveness in pediatric patients have not been established.
== '''What are the active and inactive ingredients in this medicine?''' ==
'''Active ingredient:'''
* tofersen
'''Inactive ingredients:'''
* sodium phosphate, monobasic, unspecified form
* sodium phosphate, dibasic, unspecified form
* sodium chloride
* potassium chloride
* calcium chloride
* magnesium chloride
* water
== '''Who manufactures and distributes this medicine?''' ==
'''Manufactured by:'''
* [[Biogen MA Inc.]]
* Cambridge, MA
== '''What should I know about storage and disposal of this medication?''' ==
* Store refrigerated between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.
* Do not freeze.
* If no refrigeration is available, Qalsody may be stored in its original carton, protected from light at or below 30°C (86°F) for up to 14 days.
* If removed from the original carton, unopened vials of Qalsody can be removed from and returned to the refrigerator, if necessary, for not more than 6 hours per day at or below 30°C (86°F) for a maximum of 6 days (36 hours).
Tofersen is an investigational antisense oligonucleotide designed to treat amyotrophic lateral sclerosis (ALS) associated with mutations in the superoxide dismutase 1 (SOD1) gene. It is a synthetic molecule that targets the mRNA of the SOD1 gene, aiming to reduce the production of the mutant SOD1 protein, which is implicated in the pathogenesis of ALS.
Tofersen works by binding to the mRNA of the SOD1 gene, which is responsible for encoding the SOD1 protein. By binding to this mRNA, Tofersen promotes its degradation through the recruitment of RNase H, an enzyme that cleaves the RNA strand of RNA-DNA hybrids. This process reduces the levels of SOD1 protein, particularly the mutant forms that are toxic to motor neurons.
Tofersen is currently undergoing clinical trials to evaluate its safety and efficacy in patients with SOD1-ALS. The trials are designed to assess the drug's ability to slow the progression of ALS symptoms and improve motor function. Initial studies have shown promise, with some patients experiencing stabilization of their condition.
Tofersen is administered via intrathecal injection, which involves delivering the drug directly into the cerebrospinal fluid (CSF) surrounding the spinal cord. This method of administration is chosen to ensure that the drug reaches the central nervous system, where it can exert its effects on motor neurons.
As with any investigational drug, Tofersen may have side effects. Commonly reported side effects include headache, back pain, and procedural pain associated with the intrathecal injection. More serious side effects are being monitored in clinical trials to ensure patient safety.
Research is ongoing to determine the long-term efficacy and safety of Tofersen in treating SOD1-ALS. Additionally, studies are being conducted to explore the potential of antisense oligonucleotides in treating other forms of ALS and neurodegenerative diseases.
