1) Abstract: Although Anti-sense Therapy has limitations related to targeted drug delivery, it is still considered as one of the promising technology for treating most of the Rare and Inherited disorders, being categorized as precision medicine has advanced very much with recent advances in drug delivery technologies like lipid nanoparticle (LNP) formulations, cell-targeting technologies. Anti-sense drugs are seen as most potential drugs for treating debilitating conditions with more targeted approach. The journey of Anti-sense oligonucleotides from the state of highly potential drug candidates to a sudden debacle with limitations in drug delivery and toxicity and the resume of these candidates with technological advancements will be reviewed …show more content…
The genetic mutations generally cause an over or under expression of proteins leading to a diseased condition, Anti-sense oligonucleotides can be used to modify or regulate the expression of these mal-functioning proteins which can prevent disease onset or progression. According to Mark Diamond CEO of Antisense Therapeutics, “the main advantage of Anti-Sense therapy is the ability to move relatively inexpensively and efficiently into clinical development, with platform-based advantages over existing treatments and unlike conventional drug discovery, the process for producing an antisense lead inhibitor is rapid, once the biological target is identified, many antisense sequences can be generated to its genetic sequence and tested in vitro to confirm drug potency and then studied in animals to confirm activity and safety”. These compounds can be used in treating many rare genetic diseases like Muscular Dystrophy, Spinal Muscular Atrophy, Huntington’s disease, Parkinson’s disease etc. that require much targeted approach. The application of Anti-Sense therapy for Spinal Muscular Atrophy and Huntington’s disease will be …show more content…
Spinal Muscular Atrophy (SMA)
i. Definition: Spinal Muscular Atrophy (SMA) Types I, II, and III belong to a group of hereditary diseases that cause weakness and wasting of the voluntary muscles in the arms and legs of infants and children. The disorders are caused by an abnormal or missing gene known as the survival motor neuron gene 1 (SMN1) ii. Symptoms: In SMA types 1 through 3, symptoms vary from severe to mild, based on how much SMN protein there is in the nerve cells called motor neurons. The more the SMN protein is, the milder the course of the disease is likely and symptoms show up later in life.
SMA type 1 shows symptoms from 6 months of age which include hypotonia (severely reduced muscle tone), lack of tendon reflexes, tremors and difficulty in swallowing and breathing and majority of patients die before age 2 with respiratory failure.
SMA type 2 shows symptoms between 6 and 18 months of age, children might be able to sit but unable to stand and walk without assistance, may have respiratory problems with increased risk to respiratory infections. Life expectancy is reduced but some patients can survive until
DMD also known as muscular dystrophy is muscular disease that occurs on young boys around age four to six. Muscular dystrophy is genetically transmitted disease carried from parent to offspring. This disease progressively damages or disturbs skeletal and cardiac muscle functions starting on the lower limbs. Obviously by damaging the muscle, the lower limbs and other muscles affected become very weak. This is ultimately caused by the lack dystrophin, a protein the body produces.
Duchenne Muscular Dystrophy, also known as DMD, is the most common form of muscular dystrophy. Muscular dystrophy is a condition that is inherited, and it is when muscles slowly become more and more weak and wasted. Duchenne muscular dystrophy is a form of muscular dystrophy that is very rapid and is most commonly found in boys. In muscle, there is a protein named dystrophin. Dystrophin is encoded by the DMD gene. When boys have Duchenne muscular dystrophy, they do not produce enough dystrophin in their muscles. This causes weakness in their muscles. Parents can tell if their child has duchenne muscular dystrophy by looking for various symptoms.
MS causes a degeneration of the myelin around axons due to the killing off of oligodendrocytes, which are cells that make up the myelin sheath of an axon; losing myelin decreases the neuron’s ability to propagate an action potential. Since this disease affects the central nervous system, MS can cause dysfunction of both the sensory and the motor aspects of the body. Some common sensory complaints(Lundy-Ekman, 2007) of MS are tingling, numbness, and/or paresthesia in the affected area, which is variable but typically involves one or more limbs (Palace, 2001), as well as partial blindness in one eye, a decrease in vision acuity, and double vision. Lhermitte’s sign, which is a radiating shock that travels down the back or limbs, is another common characteristic of MS that aff...
Muscular Dystrophy is a diverse group of disease which involves the weakness and wasting of muscles and leads to many other problems in physiological system. It is because of mutation in gene related to contraction and relaxation of muscles. Although recently no perfect treatment option is available for it but in nearby future cure of this disease will be available due to advanced technology and methods like gene therapy and stem cell technology.
It is characterized by normal early growth and development followed by a slowing of development, the loss of purposeful use of the hands, slowed brain and head growth, problems with walking, seizures, and intellectual disability.
As motor neurons degenerate, this obviously means they can no longer send impulses to the muscle fibers that otherwise normally result in muscle movement. Early symptoms of ALS often include increasing muscle weakness, especially involving the arms and legs, speech, swallowing or breathing. When muscles no longer receive the messages from the motor neurons that they require to function, the muscles begin to atrophy (become smaller). Limbs begin to look thinner as muscle tissue atrophies (Choi, 1988).
3. Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS. Eric Wickstrom, Ed. Wiley-Liss, Inc., NY, 1991. pp 25-33, 35-51, 125-141.
Infantile NCL (Santavuori-Haltia disease): begins between about 6 months and 2 years of age and progresses rapidly. Affected children fail to thrive and have microcephaly. Also typical are short, sharp muscle contractions called myoclonic jerks. Initial signs of this disorder include delayed psychomotor development with progressive deterioration, other motor disorders, or seizures. The infantile form has the most rapid progression and children live into their mid childhood years.
According to National Multiple Sclerosis Society, Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain and body. The central nervous system (CNS) comprises of the brain and the spinal cord. CNS is coated and protected by myelin sheath that is made of fatty tissues (Slomski, 2005). The inflammation and damage of the myelin sheath causing it to form a scar (sclerosis). This results in a number of physical and mental symptoms, including weakness, loss of coordination, and loss of speech and vision. The way the disease affect people is always different; some people experience only a single attack and recover quickly, while others condition degenerate over time (Wexler, 2013). Hence, the diagnosis of MS is mostly done by eliminating the symptoms of other diseases. Multiple sclerosis (MS) affects both men and women, but generally, it is more common in women more than men. The disease is most usually diagnosed between ages 20 and 40, however, it can occur at any age. Someone with a family history of the disease is more likely to suffer from it. Although MS is not
Muscular Dystrophy is a genetic disorder in which your muscles drastically weaken over time. Muscles are replaced with “connective tissue,” which is more of a fatty tissue than a muscular one. The connective tissue is the tissue that is commonly found in scars, and that same tissue is incapable of movement. Although Muscular Dystrophy affects muscles in general, other types affect certain groups of muscles, and happen at different periods throughout a lifetime. For example one of the most common types, Duchenne Muscular Dystrophy, targets muscles in the upper thigh and pelvis. The disease is displayed throughout early childhood, usually between ages four and seven. This genetic disorder occurs only in boys. People have difficulty sitting up or standing and lose their ability to walk in their early teens. Sadly most people die by the age of twenty. A second common type, Becker’s Muscular Dystrophy affects the same muscles as Duchenne, but first appears in teenage years. Most people with Becker’s only live into their forties (Fallon 1824-1825).
It is estimated that 1 out of every 5,600-7,700 boys ages 5-24 have Duchene or Becker muscular dystrophy. (“Data & Statistics,” 2012 April 6) Muscular dystrophy is a group of genetic diseases defined by muscle fibers that are unusually susceptible to damage. There are several different types of muscular dystrophy some of which shorten the affected person’s lifespan. (“Muscular dystrophy: Types and Causes of each form,” n.d.) There is a long history of the disorder but until recently there wasn’t much knowledge of the cause. (“Muscular Dystrophy: Hope through Research,” 16 April 2014) Symptoms are obvious and can be seen as soon as a child starts walking. (“Muscular Dystrophy,” 2012 January 19) Although muscular dystrophy mostly affects boys, girls can get it too. (“Muscular Dystrophy,” 2012 January 19) There is no cure for muscular dystrophy but there are several types of therapy and most types of muscular dystrophy are still fatal. (“Muscular Dystrophy: Hope through Research,” 16 April 2014)
Early symptoms of ALS are very slight and often overlooked. They begin as simple things, such as tripping or dropping things. Twitching or cramping of muscles and abnormal fatigue of the arms and legs may soon follow, causing difficulty in daily activities, such as walking or dressing. In more advanced stages, however, shortness of breath or difficulty in breathing and swallowing ensue, until the body is completely taken over by the disease. Intellect, eye motion, bladder function, and sensation are the only abilities spared.
The body’s inflammatory process is facilitated by T-cell and B-cell responses to autoantigens within the CNS. The inflammatory process that happens within the CNS causes declining changes in the brain. Some changes include the axonal loss and immobilizing neurological damages. The remaining damage that transpires is irreversible and permanent in the brain and spinal cord. The symptoms of MS depend on the type and the severity of the disease. If the type and severity of the disease is severe then the symptoms will be more extreme. Some of the more common symptoms that are experienced include sensory symptoms; like numbness, tingling or pain, fatigue, visual disturbances, elimination problems like frequency or urgency and depression. There are many methods to diagnosing MS. There has been an increase in treatment options available and they are continuously testing new drugs yearly.
RNA Interference has been successfully applied in many fields of medicines used to treat issues such as, Parkinson’s and Lung Cancer. One study, sponsored by Alnylam Phar...
Gene therapy is the therapeutic delivery of nucleic acid into a patient’s cells as a drug to treat diseases such as Severe Combined Immunodeficiency (SCID) and Adenosine Deaminase Deficiency (ADA) and possibly cancer as well. It was first researched in 1985