Table 1 A summary of the main mechanisms of therapeutic procedures for metabolic diseases

Combination therapeutic procedure

A therapeutic procedure using multiple therapies to treat a single disease. Often all the therapies are pharmaceutical. It can also involve non-drug therapy, such as the combination of medications, behaviour modification, or physical procedures. The different components might act through the same or different mechanisms.

Mechanistically predicated therapeutic procedure

A therapeutic procedure which directly addresses the effects of a protein defect produced by the mutation, its structure, activity, or end product. Therapies which target the local interaction or regulatory network or pathway in which the affected protein lies are also regarded as mechanistic therapies.

Complementation therapy

A therapeutic procedure in which a treatment directly or indirectly compensates for the loss or gain of activity of a genetically defective protein within the network or pathway of which that protein is a member.

Direct complementation of a genetically defective protein

A therapeutic procedure in which a genetically defective protein is replaced by a canonical source of the same protein, genetically as in gene therapy, or by some other means of delivery, whose completion is hypothesized by a health care provider to eliminate a disorder or to alleviate the signs and symptoms of a disorder or pathological process.

Compensatory complementation of a genetically defective protein

A therapeutic procedure in which the availability, activity, stability, or turnover of a defective enzyme is modified by delivery of small or macro-molecules, or genetic or epigenetic manipulation.

Functional complementation of a genetically defective protein

A therapeutic procedure in which the composition or metabolic activity of the pathway or network in which the defective protein is found is modified, compensating for alteration of activity of that protein.

Dietary regime modification

A therapeutic procedure in which the diet is supplemented with or depleted in molecules closely related to the products or end processes of a genetically defective protein which occur as natural products in the diet.

Dietary exclusion

A therapeutic procedure in which the diet is depleted in molecules closely related to the products or end processes of a genetically defective protein, which occur naturally in the diet.

Dietary supplementation

A therapeutic procedure in which the diet is supplemented with foodstuffs containing molecules closely related to the products or end processes of a genetically defective protein, which occur naturally in the diet.

Metabolite replacement

A therapeutic procedure involving enteral, parenteral, or transdermal provision of small molecules closely related to the products or end processes of a genetically defective protein.

Activity modification of a genetically defective protein

A therapeutic procedure in which generally small molecules are delivered to the organism in order to directly increase, decrease, or alter the activity or stability of a genetically defective protein.

Symptomatic therapeutic procedure

A therapeutic procedure aimed at amelioration of one or more abnormal phenotypes generated as a consequence of a defective protein or process by a means unrelated to the immediate pathway or network environment of the defective protein. Generally working at the level of the tissue or overall organismal physiology.

Surgical or physical therapeutic procedure

A therapeutic procedure to mitigate the immediate or future effects of the presence of a genetically defective protein which involves physical conditioning or anatomical modification.

Functional complementation of a genetically defective protein by inhibition

A therapeutic procedure that inhibits a component of the pathway or network in which a genetically defective protein is found, compensating for alteration of activity of that protein.

Functional complementation of a genetically defective protein by stimulation

A therapeutic procedure that stimulates a component of the pathway or network in which a genetically defective protein is found, compensating for alteration of activity of that protein.